512 Publication(s) found
Renal System, Chronic Renal Disease, Extracellular Matrix Research, Biomarker position
25. May 2020
Hyperpolarized [1- 13 C] Alanine Production: A Novel Imaging Biomarker of Renal Fibrosis
Purpose: Renal tubulointerstitial fibrosis is strongly linked to the progressive decline of renal function seen in chronic kidney disease. State-of-the-art noninvasive diagnostic modalities are currently unable to detect the earliest changes associated with the onset of fibrosis. This study was unde…
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Journal:
Authors:
- Nielsen PM,
- Mariager CØ,
- Mølmer M,
- Sparding N,
- Genovese F,
- Karsdal MA,
- Nørregaard R,
- Bertelsen LB,
- Laustsen C,
Bone, Osteoporosis
15. May 2020
Generation of Gene-Corrected Functional Osteoclasts From Osteopetrotic Induced Pluripotent Stem Cells
Background: Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene.
Methods: IMO iPSCs were generated from a patient carrying a homozygou…
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Journal:
Authors:
- Xian X,
- Moraghebi R,
- Löfvall H,
- Fasth A,
- Henriksen K,
- Richter J,
- Woods NB,
- Moscatelli I,
Rheumatology, Osteoarthritis
12. May 2020
Characterization of the interleukin-17 Effect on Articular Cartilage in a Translational Model: An Explorative Study
Background: Osteoarthritis (OA) is a progressive, chronic disease characterized by articular cartilage destruction. The pro-inflammatory cytokine IL-17 levels have been reported elevated in serum and synovial fluid of OA patients and correlated with increased cartilage defects and bone remodeling. T…
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Journal:
Authors:
- Sinkeviciute D,
- Aspberg A,
- He Y,
- Bay-Jensen AC,
- Önnerfjord P,
Endocrinology, Obesity
4. May 2020
Dose Frequency Optimization of the Dual Amylin and Calcitonin Receptor Agonist KBP-088: Long-Lasting Improvement in Food Preference and Body Weight Loss
Dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for treatment of type 2 diabetes and obesity because of their beneficial effects on body weight, blood glucose, insulin sensitivity, and food preference, at least short-term. DACRAs activate the receptors for a prolonged time…
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Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Rheumatology, Osteoarthritis, Extracellular Matrix Research, Biomarker position
4. May 2020
Osteoarthritis: Current Molecular Biomarkers and the Way Forward
The ultimate hope of researchers and patients is a pathway to development of treatments for osteoarthritis to modify the disease process in addition to the symptoms. However, development of disease modifying drugs requires objective endpoints such as measures of joint structure, joint tissue homeost…
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Journal:
Authors:
- Kraus VB,
- Karsdal MA,
Cardiovascular System, Extracellular Matrix Research, Atherosclerosis
1. May 2020
Exploring the Role of Extracellular Matrix Proteins to Develop Biomarkers of Plaque Vulnerability and Outcome
Cardiovascular disease (CVD) is the most common cause of death in industrialized countries. One underlying cause is atherosclerosis, which is a systemic disease characterized by plaques of retained lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins in the ar…
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Journal:
Authors:
- Nielsen SH,
- Jonasson L,
- Kalogeropoulos K,
- Karsdal MA,
- Reese-Petersen AL,
- Auf dem Keller U,
- Genovese F,
- Nilsson J,
- Goncalves I,
Systemic Sclerosis, Rheumatology, Extracellular Matrix Research
28. Apr 2020
Type III, IV, and VI Collagens Turnover in Systemic Sclerosis - A Longitudinal Study
Tissue turnover, especially in the skin, is altered in systemic sclerosis (SSc), leading to tissue accumulation. The objective was to examine type III, IV, and VI collagens turnovers in SSc and investigate longitudinal alterations in relation to modified Rodnan Skin Score (mRSS). We included patient…
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Journal:
Authors:
- Juhl P,
- Bay-Jensen AC,
- Hesselstrand R,
- Siebuhr AS,
- Wuttge DM,
Rheumatology, Systemic Sclerosis, Respiratory System, Extracellular Matrix Research
23. Apr 2020
Correlation Between Serological Biomarkers of Extracellular Matrix Turnover and Lung Fibrosis and Pulmonary Artery Hypertension in Patients With Systemic Sclerosis
Objective: To determine the value of serological biomarkers of collagen degradation/turnover as serum markers of organ involvement in patients with systemic sclerosis (SSc).
Methods: Serum samples were obtained from 79 SSc patients and 19 healthy control subjects. Types I to VI collagen turnover,…
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Journal:
Authors:
- Kubo S,
- Siebuhr AS,
- Bay-Jensen AC,
- Juhl P,
- Karsdal MA,
- Satoh Y,
- Todoroki Y,
- Nakano K,
- Nakayamada S,
- Tanaka Y,
Endocrinology, Obesity, Type 2-Diabetes, Hepatic System
21. Apr 2020
The Calcitonin Receptor Plays a Major Role in Glucose Regulation as a Function of Dual Amylin and Calcitonin Receptor Agonist Therapy
Amylin treatment improves body weight and glucose control, although it is limited by a short action and need for high doses. Dual amylin and calcitonin receptor agonists (DACRAs) are dual amylin and calcitonin receptor agonists with beneficial effects beyond those of amylin. However, to what extent …
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Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Endocrinology, Obesity, Hepatic System
14. Apr 2020
The Dual Amylin and Calcitonin Receptor Agonist, KBP-066, Induces an Equally Potent Weight Loss Across a Broad Dose Range While Higher Doses May Further Improve Insulin Action
Pharmacological treatment with dual amylin and calcitonin receptor agonists (DACRAs) cause significant weight loss and improvement of glucose homeostasis. In this study, the maximally efficacious dose of the novel DACRA, KeyBiosciencePeptide (KBP)-066, was investigated. Two different rat models were…
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Journal:
Authors:
- Sonne N,
- Larsen AT,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Gastrointestinal
14. Apr 2020
The Citrullinated and MMP-degraded Vimentin Biomarker (VICM) Predicts Early Response to Anti-TNFα Treatment in Crohn's Disease
Background: In Crohn's disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor-α (TNFα) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage.
Aim: The aim of this study was to investigated whe…
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Journal:
Authors:
- Mortensen JH,
- Van Haaften WT,
- Karsdal MA,
- Bay-Jensen AC,
- Olinga P,
- Grønbæk H,
- Hvas CL,
- Manon-Jensen T,
- Dijkstra G,
- Dige A,
Extracellular Matrix Research, Hepatic System, Non-Alcoholic Fatty Liver Disease
9. Apr 2020
Collagen Biology and Non-Invasive Biomarkers of Liver Fibrosis
There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liv…
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Journal:
Authors:
- Karsdal MA,
- Daniels SJ,
- Nielsen SH,
- Bager C,
- Rasmussen DGK,
- Loomba R,
- Surabattula R,
- Villesen IF,
- Luo Y,
- Shevell D,
- Gudmann NS,
- Nielsen MJ,
- George J,
- Christian R,
- Leeming DJ,
- Schuppan D,
Rheumatology, Osteoarthritis, Extracellular Matrix Research
7. Apr 2020
Sprifermin (rhFGF18) Versus Vehicle Induces a Biphasic Process of Extracellular Matrix Remodeling in Human Knee OA Articular Cartilage Ex Vivo
Sprifermin, recombinant human fibroblast growth factor 18 (rhFGF18), induces cartilage regeneration in knees of patients with osteoarthritis (OA). We hypothesized that a temporal multiphasic process of extracellular matrix (ECM) degradation and formation underlie this effect. We aimed to characteriz…
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Journal:
Authors:
- Reker D,
- Siebuhr AS,
- Thudium CS,
- Gantzel T,
- Ladel C,
- Michaelis M,
- Aspberg A,
- Berchtold MW,
- Karsdal MA,
- Gigout A,
- Bay-Jensen AC,
Gastrointestinal, Extracellular Matrix Research
3. Apr 2020
A Fragment of Collagen Type VI alpha-3 Chain Is Elevated in Serum From Patients With Gastrointestinal Disorders
Extracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC). Measuring…
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Journal:
Authors:
- Nielsen SH,
- Mortensen JH,
- Willumsen N,
- guldager Kring Rasmussen D,
- Mogensen DJ,
- Di Sabatino A,
- Mazza G,
- Jørgensen LN,
- giuffrida P,
- Pinzani M,
- Klinge L,
- Kjeldsen J,
- Leeming DJ,
- Karsdal MA,
- Genovese F,
Renal System, Endocrinology, Type 2-Diabetes, Type 1-Diabetes
1. Apr 2020
Reduced O-GlcNAcylation and Tubular Hypoxia Contribute to the Antifibrotic Effect of SGLT2 Inhibitor Dapagliflozin in the Diabetic Kidney
Diabetic kidney disease is a worldwide epidemic, and therapies are incomplete. Clinical data suggest that improved renal outcomes by Na+-glucose cotransporter 2 inhibitor (SGLT2i) are partly beyond their antihyperglycemic effects; however, the mechanisms are still elusive. Here, we investigated the …
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Journal:
Authors:
- Hodrea J,
- Balogh DB,
- Hosszu A,
- Lenart L,
- Besztercei B,
- koszegi S,
- Sparding N,
- Genovese F,
- Wagner LJ,
- Szabo AJ,
- Fekete A,
Extracellular Matrix Research, Cardiovascular System
20. Mar 2020
Atrial Fibrillation and Cardiac Fibrosis: A Review on the Potential of Extracellular Matrix Proteins as Biomarkers
The involvement of fibrosis as an underlying pathology in heart diseases is becoming increasingly clear. In recent years, fibrosis has been granted a causative role in heart diseases and is now emerging as a major contributor to Atrial Fibrillation (AF) pathogenesis. AF is the most common arrhythmia…
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Journal:
Authors:
- Reese-Petersen AL,
- Olesen MS,
- Karsdal MA,
- Svendsen J,
- Genovese F,
Rheumatology, Osteoarthritis
15. Mar 2020
Clinical and Biochemical Factors Associated With Risk of Total Joint Replacement and Radiographic Progression in Osteoarthritis: Data From Two Phase III Clinical Trials
Objectives: Clinical trials of new disease-modifying treatments for osteoarthritis should demonstrate a positive effect on a functional outcome or reduction in joint failure in order to be considered successful. Total joint replacement (TJR) surgery may be considered as joint failure, but great vari…
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Journal:
Authors:
- Bihlet A,
- Bjerre-Bastos JJ,
- Andersen JR,
- Byrjalsen I,
- Karsdal MA,
- Bay-Jensen AC,
Respiratory System, Chronic Obstructive Pulmonary Disease, Extracellular Matrix Research
9. Mar 2020
Increased Von Willebrand Factor Processing in COPD, Reflecting Lung Epithelium Damage, Is Associated With Emphysema, Exacerbations and Elevated Mortality Risk
Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and lung tissue deterioration. Given the high vascularity of the lung, von Willebrand factor (VWF), a central component of wound healing initiation, has previously been assessed in COPD. VWF processing,…
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Journal:
Authors:
- Langholm LL,
- Rønnow S,
- bülow Sand JM,
- Leeming DJ,
- Talsinger R,
- Miller BE,
- Vestbo J,
- Karsdal MA,
- Manon-Jensen T,
Respiratory System, Extracellular Matrix Research, Biomarker position
26. Jan 2020
Lost in transition: biomarkers of remodeling in patients with asthma.
PURPOSE OF REVIEW:
'Biomarkers of remodeling' represent a loose collection of features referring to several biological adaptations of the lung to cope with stressing factors. In addition, remodel-'ing' infers a dynamic process that would require a spatiotemporal resolution. This review focuses on d…
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Journal:
Authors:
- Bahmer T,
- Sand JMB,
- Weckmann M,
Cardiovascular System
17. Jan 2020
Atrial fibrillation is associated with lean body mass in postmenopausal women.
This study investigated the association between body composition and risk of atrial fibrillation (AF) in postmenopausal women. In a retrospective analysis we assessed data from 5704 postmenopausal women (age 70.7 ± 6.5 yrs.) who in 1999-2001 participated in The Prospective Epidemiological Risk Facto…
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Journal:
Authors:
- Worm MS,
- Bager CL,
- Blair JPM,
- Secher NH,
- Riis BJ,
- Christiansen C,
- Nielsen HB,
Renal System, Chronic Renal Disease, Extracellular Matrix Research
14. Jan 2020
Imbalanced turnover of collagen type III is associated with disease progression and mortality in high-risk chronic kidney disease patients
Background
Tubulointerstitial fibrosis is a major pathological feature in chronic kidney disease (CKD) and collagen type III (COL3) is a major component of the renal fibrotic scar. We hypothesized that a dysregulated turnover of COL3 is an important determinant of CKD progression. We assessed the r…
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Journal:
Authors:
- Genovese F,
- Rasmussen DGK,
- Karsdal M,
- Jesky M,
- Ferro C,
- Fenton A,
- Cockwell P,
Hepatic System, Non-Alcoholic Steatohepatitis, Non-Alcoholic Fatty Liver Disease
6. Jan 2020
Addition of trans fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis.
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. The overlap between ALD and NAFLD suggests the existence of metabolic steatohepatitis. Development of in vivo models that reflect various aspects of human steatohepatitis is essenti…
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Authors:
- Daniels SJ,
- Leeming DJ,
- Detlefsen S,
- Bruun MF,
- Hjuler ST,
- Henriksen K,
- Hein P,
- Krag A,
- Karsdal MA,
- Nielsen MJ,
- Brockbank S,
- curwys S,
3. Jan 2020
Multinutrient Supplementation Increases Collagen Synthesis during Early Wound Repair in a Randomized Controlled Trial in Patients with Inguinal Hernia.
BACKGROUND:
Inguinal hernia disease is associated with an imbalanced collagen metabolism. Surgical stress has a negative impact on nutrients important for collagen synthesis.
OBJECTIVE:
We hypothesized that supplementation with a combination of nutrients would enhance collagen biosynthesis in i…
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Journal:
Authors:
- Kjaer M,
- Frederiksen AKS,
- Nissen NI,
- Willumsen N,
- Van Hall G,
- Jorgensen LN,
- Andersen JR,
- Årgen MS,
Hepatic System, Extracellular Matrix Research, Biomarker position
28. Dec 2019
Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-β1 Epithelial Mesenchymal Transition.
An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The development of experimental platforms able to reproduce these physio-pathological conditions is essential in order to identify …
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Journal:
Authors:
- Mazza G,
- Telese A,
- Al-Akkad W,
- Frenguelli L,
- Levi A,
- Marrali M,
- Longato L,
- Thanapirom K,
- Vilia MG,
- Lombardi B,
- Crowley C,
- Crawford M,
- Karsdal MA,
- Leeming DJ,
- Marrone G,
- Bottcher K,
- Robinson B,
- Del Rio Hernandez A,
- Tamburrino D,
- Spoletini G,
- Malago M,
- Hall AR,
- Godovac-Zimmermann J,
- Luong TV,
- De Coppi P,
- Pinzani M,
- Rombouts K,
Extracellular Matrix Research, Pancreas
24. Dec 2019
Collagen fragments quantified in serum as measures of desmoplasia associate with survival outcome in patients with advanced pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular …
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Journal:
Authors:
- Willumsen N,
- Ali SM,
- Leitzel K,
- Drabick JJ,
- Yee N,
- Polimera HV,
- Nagabhairu V,
- Krecko L,
- Ali A,
- Maddukuri A,
- Moku P,
- Poullose J,
- Menon H,
- Pancholy N,
- Costa L,
- Karsdal MA,
- Lipton A,
Hepatic System, Extracellular Matrix Research
18. Dec 2019
Is the Total Amount as Important as Localization and Type of Collagen in Liver Fibrosis Attributable to Steatohepatitis?
Is liver fibrosis just liver fibrosis? Or do the subtype of collagen, its spatial localization in the liver, its cell of origin, and the time point at which it is synthesized also matter? It is important, since the various collagen subtypes hold different informative values regarding reparative proc…
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Journal:
Authors:
- Karsdal MA,
- Detlefsen S,
- Daniels SJ,
- Nielsen MJ,
- Krag A,
- Schuppan D,
Respiratory System, Chronic Obstructive Pulmonary Disease, Extracellular Matrix Research
2. Dec 2019
End-product of fibrinogen is elevated in emphysematous chronic obstructive pulmonary disease and is predictive of mortality in the ECLIPSE cohort.
BACKGROUND:
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair process that may result in intra-airway accumulation of fibrin. Given that plasma fibrinogen is the only FDA approved biomarker that predicts mortality and COPD exacerbations, we hypothesized tha…
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Journal:
Authors:
- Manon-Jensen T,
- Langholm LL,
- Ronnow SR,
- Karsdal MA,
- Tal-Singer R,
- Vestbo J,
- Leeming DJ,
- Miller BE,
- bülow Sand JM,
Respiratory System, Lung, Chronic Obstructive Pulmonary Disease, Extracellular Matrix Research, Biomarker position
26. Nov 2019
Post-translational modifications of vimentin reflect different pathological processes associated with non-small cell lung cancer and chronic obstructive pulmonary disease.
Vimentin has shown to be highly implicated in cancer initiation and progression. Vimentin is often a target of post-translational modifications (PTMs) which can be disease specific, thus targeting these specific modifications can be of high biomarker potential. In this study we set out to evaluate t…
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Journal:
Authors:
- Nissen N,
- Karsdal MA,
- Willumsen N,
Rheumatology, Osteoarthritis, Extracellular Matrix Research
14. Nov 2019
Inflammation and joint destruction may be linked to the generation of cartilage metabolites of ADAMTS-5 through activation of toll-like receptors.
OBJECTIVE:
Links between pain and joint degradation are poorly understood. We investigated the role of activation of Toll-like receptors (TLR) by cartilage metabolites in initiating and maintaining the inflammatory loop in OA causing joint destruction.
METHODS:
Synovial membrane explants (SMEs)…
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Journal:
Authors:
- Sharma N,
- drobinski P,
- Kayed A,
- Chen Z,
- Kjelgaard-Petersen CF,
- Gantzel T,
- Karsdal MA,
- Michaels M,
- Ladel C,
- Bay-Jensen AC,
- Lindemann S,
- Thudium CS,
Cardiovascular System, Central Nervous System
6. Nov 2019
A caspase-6-cleaved fragment of Glial Fibrillary Acidic Protein as a potential serological biomarker of CNS injury after cardiac arrest.
Blood levels of Glial Fibrillary Acidic protein (GFAP) reflect processes associated with different types of CNS injury. Evidence suggests that GFAP is cleaved by caspases during CNS injury, hence positioning GFAP fragments as potential biomarkers of injury-associated processes. We set out to develop…
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Journal:
Authors:
- Jonesco DS,
- Hassager C,
- Frydland M,
- Kjærgaard J,
- Karsdal MA,
- Henriksen K,
Renal System, Chronic Renal Disease, Extracellular Matrix Research, Biomarker position
5. Nov 2019
Collagen turnover profiles in chronic kidney disease.
Renal fibrosis is a hallmark of chronic kidney disease (CKD) caused by an imbalance between formation and degradation of extracellular matrix proteins. We investigated the collagen turnover profile of 81 non-dialysis CKD stage 2-5 patients by measuring peptides reflecting formation and degradation o…
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Journal:
Authors:
- Rasmussen DG,
- Boesby L,
- Nielsen SH,
- Teepel M,
- Birot S,
- Karsdal MA,
- Kamper Al,
- Genovese F,
Rheumatology, Extracellular Matrix Research
3. Nov 2019
An Ex Vivo Tissue Culture Model of Cartilage Remodeling in Bovine Knee Explants.
Ex vivo culture systems cover a broad range of experiments dedicated to studying tissue and cellular function in a native setting. Cartilage is a unique tissue important for proper function of the synovial joint and is constituted by a dense extracellular matrix (ECM), rich in proteoglycan and type …
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Journal:
Authors:
- Thudium CS,
- Engstrom A,
- Groen SS,
- Karsdal MA,
- Bay-Jensen AC,
Hematology, Hemophilia
1. Nov 2019
Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII-deficient mice.
Vascular remodeling associated with hemophilic arthropathy (HA) may contribute to bleed propagation, but the mechanisms remain poorly understood.
OBJECTIVES:
To explore molecular mechanisms of HA and the effects of hemostasis correction on synovial vascular remodeling after joint injury in hypoc…
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Journal:
Authors:
- Cooke EJ,
- Wyseure T,
- Zhou JY,
- Gopal S,
- Nasmran CA,
- Fisch KM,
- Manon-Jensen T,
- Karsdal MA,
- Mosnier LO,
- Von Drygalski A,
Hepatic System
25. Oct 2019
A Phase 1 Trial of Autologous Macrophage Therapy for Liver Cirrhosis
Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups…
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Journal:
Authors:
- Moroni F,
- Dwyer BJ,
- Graham C,
- Pass C,
- Bailey L,
- Ritchie L,
- Mitchell D,
- Glover A,
- Lauire A,
- Doig S,
- Hargreaves E,
- Fraser AR,
- Turner ML,
- Cambpell JDM,
- McGowan NWA,
- Barry J,
- Moore JK,
- Hayes PC,
- Leeming DJ,
- Nielsen MJ,
- Musa K,
- Fallowfield JA,
- Forbes SJ,
Pancreas, Extracellular Matrix Research, Biomarker position
23. Oct 2019
Clinical value of serum hyaluronan and propeptide of type III collagen in patients with pancreatic cancer.
Hyaluronan (HA) and collagen are highly expressed in pancreatic cancer (PC) stroma. HA and collagen accumulation increase tumor interstitial fluid pressure, compromising blood flow and drug penetration. The aim of this biomarker study was to determine the clinical utility of serum HA and the propept…
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Journal:
Authors:
- Chem IM,
- Willumsen N,
- Dehlendorff C,
- Johansen AZ,
- Jensen BV,
- Hansen CP,
- Hasselby JP,
- Bojesen SE,
- Pfeiffer P,
- Nielsen Se,
- Holländer NH,
- Yilmaz Mk,
- Karsdal MA,
- Johansen JS,
Gastrointestinal, Inflammatory Bowel Disease, Extracellular Matrix Research
22. Oct 2019
The intestinal tissue homeostasis - the role of extracellular matrix remodeling in inflammatory bowel disease
Introduction: Extracellular matrix (ECM) remodeling of the intestinal tissue is important in inflammatory bowel disease (IBD) due to the extensive mucosal remodeling. There are still gaps in our knowledge as to how ECM remodeling is related to intestinal epithelium homeostasis and healing of the int…
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Journal:
Authors:
- Mortensen JH,
- Lindholm M,
- Langholm LL,
- Kjeldsen J,
- Bay-Jensen AC,
- Karsdal MA,
- Manon-Jensen T,
Hepatic System, Non-Alcoholic Fatty Liver Disease
16. Oct 2019
Improvement of non-invasive markers of NAFLD from an individualised, web-based exercise program.
BACKGROUND:
Lifestyle modifications remain the cornerstone of treatment in non-alcoholic fatty liver disease (NAFLD). However, they requently fail related to the inability of patients to implement lasting changes.
AIMS:
To evaluate the effects of a short, web-based, individualised exercise prog…
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Journal:
Authors:
- Huber Y,
- Pfirrmann D,
- Gebhardt I,
- Labenz C,
- Gehrke N,
- Straub C,
- Ruckes C,
- Bantel H,
- Belda E,
- Clément K,
- Leeming DJ,
- Karsdal MA,
- Galle PR,
- Simon P,
- Schattenberg JM,
Hepatic System, Biomarker position
16. Oct 2019
Serum markers of type III and IV procollagen processing predict recurrence of fibrosis in liver transplanted patients.
Following liver transplantation (LT), 10-30% of patients develop recurrent cirrhosis (RC). There is an urgent need for predictive non-invasive markers for improved monitoring of these patients. Here we studied extracellular matrix biomarkers as predictors of RC after LT. Forty-seven LT patients were…
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Journal:
Authors:
- Nielsen MJ,
- Villesen IF,
- Gudmann NS,
- Leeming DJ,
- Krag A,
- Karsdal MA,
- Zimmermann T,
- Schuppan D,
Rheumatology, Clinical Data Quality, Osteoarthritis
8. Oct 2019
Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial.
IMPORTANCE:
Sprifermin is under investigation as a disease-modifying osteoarthritis drug.
OBJECTIVE:
To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis.
DESIGN, SETTING, AND PARTICIPANT…
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Journal:
Authors:
- Hochberg MC,
- Guermazi A,
- Guehring H,
- Aydemir A,
- Wax S,
- Fleuranceau-Morel P,
- Reinstrup Bihlet A,
- Byrjalsen I,
- Ragnar Andersen J,
- Eckstein F,
Rheumatology, Bone, Osteoporosis, Osteoarthritis, Biomarker position
30. Sep 2019
Biochemical markers in osteoarthritis with lessons learned from osteoporosis.
Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th…
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Journal:
Authors:
Endocrinology, Type 1-Diabetes, Renal System, Cardiovascular System
13. Sep 2019
Markers of Collagen Formation and Degradation Reflect Renal Function and Predict Adverse Outcomes in Patients With Type 1 Diabetes.
OBJECTIVE:
Patients with type 1 diabetes (T1D) have a higher risk of developing chronic kidney disease, cardiovascular events (CVEs), and mortality than the general population. We hypothesized that two previously published biomarkers, namely PRO-C6, a biomarker of collagen type VI formation, and C3…
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Journal:
Authors:
- Pilemann-Lyberg S,
- Rasmussen DG,
- Hansen TW,
- Tofte N,
- Winther SA,
- Holm Nielsen S,
- Theilade S,
- Karsdal MA,
- Genovese F,
- Rossing P,
Rheumatology, Osteoarthritis, Biomarker position, Bone
3. Sep 2019
Associations between biomarkers of bone and cartilage turnover, gender, pain categories and radiographic severity in knee osteoarthritis.
BACKGROUND:
Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee j…
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Journal:
Authors:
- Bihlet AR,
- Byrjalsen I,
- Bay-Jensen AC,
- Andersen JR,
- Christiansen C,
- Riis BJ,
- Karsdal MA,
Extracellular Matrix Research, Biomarker position, Breast
15. Aug 2019
Clinical Relevance of Collagen Protein Degradation Markers C3M and C4M in the Serum of Breast Cancer Patients Treated with Neoadjuvant Therapy in the GeparQuinto Trial.
Background: Remodeling of extracellular matrix through collagen degradation is a crucial step in the metastatic cascade. The aim of this study was to evaluate the potential clinical relevance of the serum collagen degradation markers (CDM) C3M and C4M during neoadjuvant chemotherapy for breast cance…
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Journal:
Authors:
- Banys-Paluchowski M,
- Loibl S,
- Witzel I,
- Mundhenke C,
- Lederer B,
- Solbach C,
- Karn T,
- Marmé F,
- Nekljudova V,
- Schem C,
- Stickeler E,
- Willumsen N,
- Karsdal MA,
- Untch M,
- Müller V,
Rheumatology, Spondyloarthropathies, Biomarker position
2. Aug 2019
Metabolites of type I, II, III, and IV collagen may serve as markers of disease activity in axial spondyloarthritis.
Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A…
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Journal:
Authors:
- Husakova M,
- Bay-Jensen AC,
- forejtová S,
- Zegzulkova K,
- Tomcik M,
- gregová M,
- Bubová K,
- Horínková J,
- Gatterová J,
- Pavelka K,
- Siebuhr AS,
Rheumatology, Osteoarthritis, Rheumatoid Arthritis
24. Jul 2019
Identification of pathological RA endotypes using blood-based biomarkers reflecting tissue metabolism. A retrospective and explorative analysis of two phase III RA studies.
There is an increasing demand for accurate endotyping of patients according to their pathogenesis to allow more targeted treatment. We explore a combination of blood-based joint tissue metabolites (neoepitopes) to enable patient clustering through distinct disease profiles. We analysed data from two…
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Journal:
Authors:
- Blair JPM,
- Bager C,
- Karsdal MA,
- Bay-Jensen AC,
Respiratory System, Biomarker position, Extracellular Matrix Research, Idiopathic Pulmonary Fibrosis
12. Jul 2019
Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort.
Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was ass…
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Journal:
Authors:
- Orlan LA,
- Duggan AR,
- Oballa E,
- Taggart SC,
- Simpson JK,
- Kang'ombe AR,
- Braybrooke R,
- Molyneaux PL,
- North B,
- Karkera Y,
- Leeming DJ,
- Karsdal MA,
- Nanthakumar CB,
- Fahy WA,
- Marshall RP,
- Jenkins RG,
- Maher TM,
Hepatic System, Extracellular Matrix Research
11. Jul 2019
Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART
Abstract
Background and aims
Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recen…
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Journal:
Authors:
- Dold L,
- Nielsen MJ,
- Praktiknjo M,
- Schwarzer-Zander C,
- Boesecke C,
- Schierwagen R,
- Mohr R,
- Wasmuth JC,
- Jansen C,
- Bischoff J,
- Rockstroh J,
- Karsdal MA,
- Trebicka J,
- Leeming DJ,
Extracellular Matrix Research, Hepatic System, Non-Alcoholic Fatty Liver Disease
4. Jul 2019
Performance of the PRO-C3 collagen neo-epitope biomarker in non-alcoholic fatty liver disease.
There is an unmet need for non-invasive biomarkers in non-alcoholic fatty liver disease (NAFLD) that can diagnose advanced disease and identify patients suitable for clinical trials. The PRO-C3 collagen neo-epitope is a putative direct marker of fibrogenesis. We assessed the performance of PRO-C3 in…
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Journal:
Authors:
- Boyle M,
- tiniakos D,
- Schattenberg JM,
- Ratziu V,
- Bugianessi E,
- Petta S,
- Oliveira CP,
- Govaere O,
- Yournes R,
- McPherson S,
- Bedossa P,
- Nielsen MJ,
- Karsdal M,
- Leeming D,
- Kendrick S,
- Anstee QM,
Obesity, Endocrinology
1. Jul 2019
The Dual Amylin and Calcitonin Receptor Agonist KBP-088 Induces Weight Loss and Improves Insulin Sensitivity Superior to Chronic Amylin Therapy
KBP-088 (KeyBiosciencePeptide 088) is a potent dual amylin and calcitonin receptor agonist (DACRA). DACRAs are known to elicit potent activity in terms of typical amylin-induced responses, such as reducing food intake and body weight. However, to what extent amylin infusion can mimic the effects of …
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Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Gehring K,
- Karsdal MA,
- Henriksen K,
Hepatic System, Endocrinology, Type 2-Diabetes
1. Jul 2019
Use of Plasma Fragments of Propeptides of Type III, V, and VI Procollagen for the Detection of Liver Fibrosis in Type 2 Diabetes
OBJECTIVE:
This study assessed the utility of plasma fragments of propeptides of type III (PRO-C3), V (PRO-C5), and VI (PRO-C6) procollagen for the detection of liver fibrosis in patients with type 2 diabetes mellitus (T2DM).
RESEARCH DESIGN AND METHODS:
Patients with T2DM (n = 191) underwent a…
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Journal:
Authors:
- Bril F,
- Leeming DJ,
- Karsdal MA,
- Kalavalapalli S,
- Darb D,
- Lai J,
- Rabe M,
- Cusi K,
Rheumatology, Osteoarthritis
26. Jun 2019
Incidence of total hip and total knee replacements from the prospective epidemiologic risk factor study: considerations for event driven clinical trial design
BACKGROUND:
Osteoarthritis (OA) leads to joint failure and total joint replacement (TJR, either hip (H) or knee (K)). Worsening of pain and joint space narrowing are believed to be surrogates for joint failure; however, we hypothesize that TJR, as a reflection of joint failure, can be used as an en…
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Journal:
Authors:
Osteoporosis, Bone
10. Jun 2019
Hematopoietic stem cell-targeted neonatal gene therapy with a clinically applicable lentiviral vector corrects osteopetrosis in oc/oc mice.
Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by nonfunctional osteoclasts. Approximately 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. Gene therapy represents a potential alternative treatment …
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Journal:
Authors:
- Löfvall H,
- Rothe M,
- Schambach A,
- Henriksen K,
- Richter J,
- Moscatelli I,
Bone, Rheumatology, Osteoarthritis
5. Jun 2019
A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model
OBJECTIVES:
Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor a…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Lövfall H,
- Karsdal MA,
- Andreassen KV,
- Thudium CS,
- Henriksen K,
1. Jun 2019
Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease.
BACKGROUND AND AIMS:
Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot forma…
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Journal:
Authors:
- Sun S,
- Karsdal MA,
- Mortensen JH,
- Luo Y,
- Kjeldsen J,
- Krag A,
- Jensen MD,
- Bay-Jensen AC,
- Manon-Jensen T,
31. May 2019
Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest
Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome.
Methods: Sing…
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Journal:
Authors:
- Grand J,
- Kjaergaard J,
- Nielsen N,
- Friberg H,
- Crongerg T,
- Bro-Jeppesen J,
- Karsdal MA,
- Nielsen HB,
- Frydland M,
- Henriksen K,
- Matsson N,
- Zetterberg H,
- Hassager C,
Bone, Bone
28. May 2019
Low bone turnover levels predict increased risk of cancer
BACKGROUND:
Several epidemiological studies have shown an association between bone mineral density (BMD) and risk of breast cancer in postmenopausal women, but it remains unknown whether bone turnover is associated with increased risk of cancer. The aim of this study was to investigate if markers o…
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Journal:
Authors:
- Bager CL,
- Bay F,
- Christiansen C,
- Karsdal MA,
Endocrinology
23. May 2019
Circulating Biomarkers of Testosterone's Anabolic Effects on Fat-Free Mass
BACKGROUND:
Biomarkers that predict response to anabolic therapies could expedite the development of function promoting anabolic drugs. This study aimed to identify serum biomarkers that are responsive to testosterone administration and associated with increases in fat-free mass (FFM).
METHODS:
…
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Journal:
Authors:
- Huang G,
- Rocha GV,
- Pencina KM,
- Cox K,
- Krishnan V,
- Henriksen K,
- Mitchell P,
- Sissons SE,
- Li Z,
- Nedergaard AF,
- Karsdal MA,
- Sun S,
- Storer TW,
- Basaria S,
- Bhasin S,
Cardiovascular System, Respiratory System
17. May 2019
Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone
Cardiac fibrosis contributes to the development of heart failure in pulmonary hypertension. We aimed to assess the development of fibrosis and the effects of treatment with the anti-fibrotic agent pirfenidone in pressure overload induced right ventricular (RV) failure. Wistar rat weanlings were rand…
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Journal:
Authors:
- Andersen S,
- Axelsen JB,
- Ringgaard S,
- Nyengaard JR,
- Holm Nielsen S,
- Genovese F,
- Karsdal MA,
- Hyldebrandt JA,
- Sørensen CB,
- de Man FS,
- Jan Bogaard H,
- Nielsen-kudsk JE,
- Andersen A,
12. May 2019
Matrix Metalloprotease Generated Fragments of Type VI Collagen Have Serum Biomarker Potential in Cancer - A Proof of Concept Study
BACKGROUND:
Type VI collagen (COL6) is associated with several pro-tumorigenic events. COL6 is primarily composed of three alpha-chains (a1-a3) forming a specialized microfibrillar network to support tissue architecture. COL6 homeostasis is lost in the tumor due to increased COL6 synthesis by activ…
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Journal:
Authors:
- Willumsen N,
- Karsdal MA,
- Bager C,
29. Mar 2019
Cancer risk in relation to body fat distribution, evaluated by DXA-scans, in postmenopausal women - the Prospective Epidemiological Risk Factor (PERF) study
Studies with direct measures of body fat distribution are required to explore the association between central and general obesity to cancer risk in postmenopausal women. This study investigates the association between central obesity and general obesity to overall/site-specific cancer risk in postme…
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Journal:
Authors:
- Stanstrup LM,
- Nielsen HB,
- Pedersen BK,
- Karsdal MA,
- Blair JPM,
- Christensen JF,
- Bager CL,
Respiratory System, Chronic Obstructive Pulmonary Disease
9. Mar 2019
Specific elastin degradation products are associated with poor outcome in the ECLIPSE COPD cohort
Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an es…
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Journal:
Authors:
- Ronnow SR,
- Langholm LL,
- Sand JMB,
- Thoracius-Ussing J,
- Leeming DJ,
- Manon-Jensen T,
- Tal-Singer R,
- Miller BE,
- Karsdal MA,
- Vestbo J,
Oncology
6. Mar 2019
Collagens and Cancer associated fibroblasts in the reactive stroma and its relation to Cancer biology
The extracellular matrix (ECM) plays an important role in cancer progression. It can be divided into the basement membrane (BM) that supports epithelial/endothelial cell behavior and the interstitial matrix (IM) that supports the underlying stromal compartment. The major components of the ECM are th…
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Authors:
- Nissen N,
- Karsdal MA,
- Willumsen N,
Hepatic System, Non-Alcoholic Steatohepatitis
1. Mar 2019
Biochemical and histological characterisation of an experimental rodent model of non-alcoholic steatohepatitis - Effects of a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist and a glucagon-like peptide-1 analogue
BACKGROUND:
Non-alcoholic steatohepatitis (NASH) is a prevalent disease that is highly associated with the metabolic syndrome and type II diabetes. The development of in vivo models that reflect all nuances of the human NASH pathology is essential for drug discovery and development. We aimed to fur…
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Journal:
Authors:
- Daniels SJ,
- Leeming DJ,
- Detlefsen S,
- Bruun MF,
- Hjuler ST,
- Henriksen K,
- Hein P,
- Karsdal MA,
- Brockbank S,
- Cruwys S,
Rheumatology, Systemic Sclerosis
1. Mar 2019
Association of metabolites reflecting type III and VI collagen formation with modified Rodnan skin score in systemic sclerosis - a cross-sectional study
OBJECTIVE:
The objective was to investigate blood-based biomarkers of type I (PRO-C1), III (PRO-C3) and VI (PRO-C6) collagen formation in systemic sclerosis (SSc) patients and examine their correlation to modified Rodnan skin score (mRSS).
METHODS:
Limited (lSSc, n = 76) and diffuse SSc (dSSc, …
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Journal:
Authors:
- Juhl P,
- Vinderslev Iversen L,
- Karlsmark T,
- Karsdal MA,
- Bay-Jensen AC,
- Mogensen M,
- Siebuhr AS,
Rheumatology, Bone
28. Feb 2019
GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro
C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe…
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Journal:
Authors:
- Löfvall H,
- Katri A,
- Dabrowska A,
- Karsdal MA,
- Luo Y,
- He Y,
- Manon-Jensen T,
- Dziegiel MH,
- Bay-Jensen AC,
- Thudium CS,
- Henriksen K,
Rheumatology, Rheumatoid Arthritis, Bone
22. Feb 2019
Combining Naproxen and a Dual Amylin and Calcitonin Receptor Agonist improves pain and structural outcomes in the Collagen-Induced Arthritis rat model
BACKGROUND:
Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction w…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Löfvall H,
- Ding M,
- Karsdal MA,
- Andreassen KV,
- Schneider Thudium C,
- Henriksen K,
Hepatic System, Gastrointestinal
12. Feb 2019
Enhanced processing of von Willebrand factor reflects disease severity and discriminates severe portal hypertension in cirrhosis
OBJECTIVES:
Portal hypertension in cirrhosis is associated with endothelial dysfunction, impaired wound healing, and decreased platelet count. Increased von Willebrand factor (VWF) formation has been suggested as a compensatory mechanism, but the role of VWF processing has not been directly assesse…
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Journal:
Authors:
- Langholm LL,
- Manon-Jensen T,
- Karsdal MA,
- Bendtsen F,
- Leeming DJ,
- Møller S,
Extracellular Matrix Research, Respiratory System, Idiopathic Pulmonary Fibrosis, Lung, Chronic Obstructive Pulmonary Disease
12. Feb 2019
Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders
OBJECTIVES:
Remodeling of the extracellular matrix (ECM) is a key event in different lung disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-SMA, which …
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Journal:
Authors:
- Holm Nielsen S,
- Willumsen N,
- Leeming DJ,
- Daniels SJ,
- brix s,
- Karsdal MA,
- Genovese F,
- Nielsen MJ,
Rheumatology, Spondyloarthropathies
11. Feb 2019
Metabolites of C-reactive protein and vimentin are associated with disease activity of axial spondyloarthritis.
OBJECTIVES:
Non-radiographic (nr-axSpA) and radiographic (AS) forms of axial spondyloarthritis (axSpA) share clinical features, but have different radiographic patterns. Radiographic progression is not associated with the current disease activity biomarkers. We investigated a matrix metalloproteina…
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Journal:
Authors:
- Siebuhr AS,
- Husakova M,
- forejtová S,
- Zegzulkova K,
- Tomcik M,
- Urbanova M,
- Grobelna K,
- Gatterova J,
- Bay-Jensen AC,
- Pavelka K,
Hepatic System, Extracellular Matrix Research, Renal System
9. Feb 2019
Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis
BACKGROUND & AIMS:
Remodelling of extracellular matrix is crucial in progressive liver fibrosis. Collagen type III desposition has been shown in acute decompensation. Extratracellular matrix is compiled of deposition of various components. The role of basement membrane collagen type IV in advanced …
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Journal:
Authors:
- Lehmann J,
- Praktiknjo M,
- Nielsen MJ,
- Schierwagen R,
- Meyer C,
- Thomas D,
- Violi F,
- Strassburg CP,
- Bendtsen F,
- Møller S,
- Krag A,
- Karsdal M,
- Leeming DJ,
- Trebicka J,
Rheumatology, Osteoarthritis
31. Jan 2019
Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development
PURPOSE OF REVIEW:
This review focuses on the molecular taxonomy of osteoarthritis from the perspective of molecular biomarkers. We discuss how wet biochemical markers may be used to understand disease pathogenesis and progression and define molecular endotypes of osteoarthritis and how these corre…
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Journal:
Authors:
- mobasheri A,
- Van Spil WE,
- Budd E,
- Uzieliene I,
- Bernotiene E,
- Bay-Jensen AC,
- Larkin J,
- Levesque MC,
- Gualillo O,
- Henrotin Y,
Gastrointestinal, Inflammatory Bowel Disease
31. Jan 2019
Initiation of the Wound Healing Cascade in Inflammatory Bowel Disease: Assessment of Von Willebrand Factor ADAMTS-13 Processing and Formation in Crohn’s Disease
Background: Crohn’s disease (CD) is a chronic inflammatory condition of the intestinal tract resulting in severe intestinal tissue
damage. The concept of mucosal healing has therefore gained significant interest as a therapeutic end point in the treatment of
inflammatory bowel disease (IBD). Given…
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Authors:
- Manon-Jensen T,
- Langholm LL,
- Sun S,
- Mortensen JH,
- He Y,
- Krag A,
- Jensen MD,
- Bay-Jensen AC,
- Kjeldsen J,
- Karsdal MA,
Rheumatology, Osteoarthritis, Rheumatoid Arthritis
14. Jan 2019
Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis.
OBJECTIVE:
Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of OA, of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type X collagen t…
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Journal:
Authors:
- He Y,
- Manon-Jensen T,
- Arendt-Nielsen L,
- Petersen KK,
- Christiansen T,
- Samuels J,
- Abramson S,
- Karsdal MA,
- Attur M,
- Bay-Jensen AC,
Oncology, Colorectal
9. Jan 2019
Vastatin (the NC1 domain of human type VIII collagen a1 chain) is linked to stromal reactivity and elevated in serum from patients with colorectal cancer.
Vastatin, a fragment derived from type VIII collagen, is one of the least studied collagen-derived matrikines. Vastatin can be detected in serum but little is known regarding the relevance of serum vastatin in colorectal cancer (CRC). In this study, serum vastatin was measured (ELISA) in 67 healthy …
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Journal:
Authors:
- will,
- Jorgensen LN,
- Karsdal MA,
Idiopathic Pulmonary Fibrosis, Respiratory System, Oncology, Lung, Extracellular Matrix Research
2. Jan 2019
The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis.
Myofibroblasts are the key effector cells responsible for excessive extracellular matrix deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). The PI3K/Akt/mTOR axis has been implicated in fibrosis, with pan-PI3K/mTOR inhibition currently under clinical evaluatio…
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Journal:
Authors:
- Woodcock HV,
- Eley JD,
- Platé M,
- Manthakumar CB,
- Martufi M,
- Peace S,
- Joberty G,
- Poeckel D,
- Good RB,
- Taylor AR,
- Zinn N,
- Redding M,
- Forty EJ,
- Hynds RE,
- Santon C,
- Karsdal MA,
- Maher TM,
- Bergamini G,
- Marshall RP,
- Blanchard AD,
- Mercer PF,
- Chambers RC,
Oncology
19. Dec 2018
Non-invasive biomarkers derived from the extracellular matrix associate with response to immune checkpoint blockade (anti-CTLA-4) in metastatic melanoma patients
BACKGROUND:
Excessive extracellular matrix (ECM) remodeling and a reactive stroma can affect T-cell infiltration and T-cell activity in the tumor and hereby influence response to immune checkpoint inhibitors (ICI). In the pursuit of finding biomarkers that predict treatment response, we evaluated t…
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Journal:
Authors:
- Jensen C,
- Madsen DH,
- Hansen M,
- Schmidt H,
- Svane IM,
- Karsdal MA,
- Willumsen N,
Oncology
19. Dec 2018
Non-invasive biomarkers derived from the extracellular matrix associate with response to immune checkpoint blockade (anti-CTLA-4) in metastatic melanoma patients (1)
Background
Excessive extracellular matrix (ECM) remodeling and a reactive stroma can affect T-cell infiltration and T-cell activity in the tumor and hereby influence response to immune checkpoint inhibitors (ICI). In the pursuit of finding biomarkers that predict treatment response, we evaluated th…
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Journal:
Authors:
- Jensen C,
- Madsen D,
- Hansen M,
- Schmidt H,
- Svane IM,
Oncology, Extracellular Matrix Research
19. Dec 2018
Non-invasive biomarkers derived from the extracellular matrix associate with response to immune checkpoint blockade (anti-CTLA-4) in metastatic melanoma patients.
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Journal:
Authors:
- jensen C,
- Madsen DH,
- hansen M,
- Schmidt H,
- Svane IM,
- Karsdal MA,
- Willumsen N,
Rheumatology, Osteoarthritis
18. Dec 2018
Serological biomarker profiles of rapidly progressive osteoarthritis in tanezumab-treated patients.
There is a need for efficacious and safe pain treatments for OA (osteoarthritis). The nerve growth factor (NGF) antibody tanezumab is associated with high efficacy, but when combined with chronic NSAID treatment shows an increased risk of rapidly progressive osteoarthritis (RPOA) in a small group of…
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Journal:
Authors:
- Karsdal MA,
- Verburg KM,
- West CR,
- Bay-Jensen AC,
- Keller DS,
- Arends RHGP,
Renal System, Extracellular Matrix Research
7. Dec 2018
A non-invasive biomarker of type III collagen degradation reflects ischaemia reperfusion injury in rats.
BACKGROUND:
Maintenance of kidney function in kidney allografts remains a challenge, as the allograft often progressively develops fibrosis after kidney transplantation. Fibrosis is caused by the accumulation of extracellular matrix proteins like type I and III collagen (COL I and III) that replace…
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Journal:
Authors:
- Rasmussen DG,
- Nielsen PM,
- Kasab-Oglo ôY,
- Nielsen SH,
- kerulf-Lassen C,
- Karsdal MA,
- Genovese F,
- Nørregaard R,
Rheumatology, Systemic Sclerosis, Extracellular Matrix Research
3. Dec 2018
Serum biomarkers of collagen turnover as potential diagnostic tools in diffuse systemic sclerosis: A cross-sectional study
BACKGROUND:
Systemic sclerosis (SSc) is characterized by excessive fibrosis throughout the body. This leads to the release of extracellular matrix (ECM) fragments into circulation, where they may be quantified as biomarkers. The objectives were to investigate levels of ECM turnover biomarkers and t…
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Journal:
Authors:
- Juhl P,
- Bay-Jensen AC,
- Karsdal MA,
- Siebuhr AS,
- Franchimont N,
- Chavez J,
Respiratory System, Idiopathic Pulmonary Fibrosis, Oncology, Lung
30. Nov 2018
A serological marker of the N-terminal neoepitope generated during LOXL2 maturation is elevated in patients with cancer or idiopathic pulmonary fibrosis
OBJECTIVES:
Lysyl oxidase like 2 (LOXL2) is associated with poor prognosis in idiopathic pulmonary disease (IPF) and cancer. We developed an Enzyme-linked immunosorbent assay (ELISA) targeting the LOXL2 neo-epitope generated through the release of the signal peptide during LOXL2 maturation.
DESI…
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Journal:
Authors:
- Leeming DJ,
- Willumsen N,
- Sand JM,
- Holm Nielsen S,
- Dasgupta B,
- Brodmerkel C,
- Bager CL,
- Karsdal MA,
Oncology, Lung
22. Nov 2018
Non-invasive profiling of protease-specific elastin turnover in lung cancer: biomarker potential.
PURPOSE:
Elastin is a signature protein of lungs. Increased elastin turnover driven by altered proteolytic activity is an important part of lung tumorigenesis. Elastin-derived fragments have been shown to be pro-tumorigenic, however, little is known regarding the biomarker potential of such elastin…
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Authors:
- Thoracius-Ussing J,
- Kehlet SN,
- Rønnow S,
- Karsdal MA,
- Willumsen N,
Rheumatology, Extracellular Matrix Research, Systemic Sclerosis
20. Nov 2018
Citrullinated Vimentin and biglycan protein fingerprints as candidate serological biomarkers for disease activity in systemic sclerosis: A pilot study.
PURPOSE:
Extracellular matrix (ECM) deposition and remodelling in skin and lungs of systemic sclerosis (SSc) subjects lead to release of metabolites/biomarkers into circulation. We investigated if biomarkers of ECM degradation (biglycan and elastin) and macrophage activation (citrullinated vimentin…
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Journal:
Authors:
- Siebuhr AS,
- Juhl P,
- Bay-Jensen AC,
- Karsdal MA,
- Franchimont N,
- Chavez JC,
Rheumatology, Osteoarthritis
19. Nov 2018
Proposed study designs for approval based on a surrogate endpoint and a post-marketing study under FDA's accelerated approval regulations for disease modifying osteoarthritis drugs
In 1992, the Food and Drug Administration (FDA) instituted the accelerated approval regulations that allow drugs or biologics for serious conditions that fill an unmet medical need to be approved on the basis of a surrogate endpoint or an intermediate clinical endpoint. The current definition of a s…
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Journal:
Authors:
- Kraus VB,
- Simon LS,
- Katz JN,
- Neogi T,
- Hunter D,
- Guermazi A,
- Karsdal MA,
Cardiovascular System, Myocardial Fibrosis, Acute Myocardial Infarct, Extracellular Matrix Research
19. Nov 2018
Cathepsin K-deficiency impairs mouse cardiac function after myocardial infarction.
BACKGROUND:
Extracellular matrix metabolism and cardiac cell death participate centrally in myocardial infarction (MI). This study tested the roles of collagenolytic cathepsin K (CatK) in post-MI left ventricular remodeling.
METHODS AND RESULTS:
Patients with acute MI had higher plasma CatK lev…
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Journal:
Authors:
- Fang W,
- He A,
- Xiang MX,
- Lin Y,
- Wang Y,
- Li J,
- Yang C,
- Zhang X,
- Liu CL,
- Sukhova GK,
- Barascuk N,
- Larsen L,
- Karsdal MA,
- Libby P,
- Shi GP,
Rheumatology, Rheumatoid Arthritis
7. Nov 2018
The VICM biomarker is released from activated macrophages and inhibited by anti-GM-CSFRα-mAb treatment in rheumatoid arthritis patients.
OBJECTIVES:
Macrophages possess widespread pro-inflammatory, destructive, and remodelling capabilities that can critically contribute to acute and chronic diseases, such as rheumatoid arthritis (RA). Continuous monitoring and measurement of selective counteraction of macrophage activity in patients…
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Journal:
Authors:
- Mortensen JH,
- Guo X,
- De Los Reyes M,
- Dziegiel MH,
- Bay Jensen AC,
- White WI,
Rheumatology, Osteoarthritis
6. Nov 2018
A Novel High Sensitivity Type II Collagen Blood-Based Biomarker, PRO-C2, for Assessment of Cartilage Formation
N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH₂-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utili…
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Journal:
Authors:
- Luo Y,
- He Y,
- Gudmann NS,
- Henriksen K,
- Simonsen O,
- Ladel C,
- Michaels M,
- Mobasheri A,
- Karsdal MA,
- Bay-Jensen AC,
Cardiovascular System, Atherosclerosis
6. Nov 2018
Markers of Basement Membrane Remodeling Are Associated With Higher Mortality in Patients With Known Atherosclerosis.
Background Patients with atherosclerosis have a high risk of cardiovascular events and death. Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix proteins in the intima. We hypothesized that dysregulated remodeling of the basement membrane proteins may be assoc…
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Journal:
Authors:
- Nielsen SH,
- Tengryd C,
- Edsfeldt A,
- Brix S,
- Genovese F,
- Bengtsson E,
- Karsdal MA,
- Leeming DJ,
- Nilsson J,
- Goncalves I,
Renal System, Endocrinology
16. Oct 2018
RAAS inhibitors directly reduce diabetes-induced renal fibrosis via growth factor inhibition
KEY POINTS:
Increased activation of the renin-angiotensin-aldosterone system (RAAS) and elevated growth factor production are of crucial importance in the development of renal fibrosis leading to diabetic kidney disease. The aim of this study was to provide evidence for the antifibrotic potential o…
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Journal:
Authors:
- koszegi S,
- Molnar A,
- Lenart L,
- Hodrea J,
- Balogh DB,
- Lakat T,
- Szkibinszjik J,
- Hoszu A,
- Sparding N,
- Fenovese F,
- Wagner L,
- Vannay A,
- Szabo AJ,
- Fekete A,
Bone, Extracellular Matrix Research
2. Oct 2018
Alterations in non-type I collagen biomarkers in osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a rare disorder of connective tissue caused by abnormalities in the synthesis or processing of type I collagen. Type I collagen is the most abundant type of collagen and is expressed in almost all connective tissues. Given that type I collagen interacts with other col…
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Journal:
Authors:
- Nicol L,
- Morar P,
- Wang Y,
- Henriksen K,
- Sun S,
- Karsdal MA,
- Smith R,
- Nagamani SCS,
- Shapiro J,
- Lee B,
- Orwoll E,
Respiratory System, Chronic Obstructive Pulmonary Disease
1. Oct 2018
Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease.
BACKGROUND:
The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology-related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of t…
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Journal:
Authors:
- Schuppan D,
- Leeming DJ,
- papakonstantinou E,
- Kostikas K,
- Boersma W,
- Louis R,
- Milenkovik B,
- Aerts J,
- Sand JM,
- Wouters EFM,
- Rohde G,
- Prat C,
- Torres A,
- Welte T,
- Tamm M,
- Karsdal M,
- Stolz D,
Renal System, Chronic Renal Disease, Extracellular Matrix Research
1. Oct 2018
A novel biomarker of laminin turnover is associated with disease progression and mortality in chronic kidney disease.
BACKGROUND:
Patients with chronic kidney disease (CKD) have increased risk of development of end-stage renal disease (ESRD) and early mortality. Fibrosis is the central pathogenic process in CKD and is caused by dysregulated extracellular matrix (ECM) remodeling. The laminin γ1 chain (LAMC1) is a c…
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Journal:
Authors:
- Holm Nielsen S,
- guldager Kring Rasmussen D,
- Brix S,
- Jesky M,
- Fenton A,
- Ferro CJ,
- Karsdal MA,
- Genovese F,
- Cockwell P,
Cardiovascular System
11. Sep 2018
Cardiac magnetic resonance using late gadolinium enhancement and atrial T1 mapping predicts poor outcome in patients with atrial fibrillation after catheter ablation therapy
To determine the pre-procedural value of different fibrotic biomarkers and comprehensive cardiac magnetic resonance (CMR) for the prediction of poor response to ablation therapy in patients with atrial fibrillation (AF). Left atrial (LA) late gadolinium enhancement (LGE) and native LA T1 relaxation …
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Journal:
Authors:
- Luetkens JA,
- Wolpers AC,
- Beiert T,
- Kuetting D,
- Dabir D,
- Homsi R,
- Meemdermann H,
- Day'e NA,
- Knappe V,
- Karsdal MA,
- Nielsen SH,
- Genovese F,
- Stöckjgt F,
- Linhart M,
- Thomas D,
- Nickenig G,
- Schild HH,
- Schrickel JW,
- Andrié RP,
Chronic Obstructive Pulmonary Disease, Respiratory System
10. Sep 2018
Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio…
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Journal:
Authors:
- Gudmann NS,
- Manon-Jensen T,
- Sand JMB,
- Diefenbach C,
- Sun S,
- Danielsen A,
- Karsdal MA,
- Leeming DJ,
Respiratory System, Chronic Obstructive Pulmonary Disease
10. Sep 2018
Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio…
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Journal:
Authors:
- Gudmann NS,
- Manon-Jensen T,
- Sand JM,
- Diefenbach C,
- Sun S,
- Danielsen A,
- Karsdal MA,
- Leeming DJ,
Rheumatology, Osteoarthritis
7. Sep 2018
IL-37 diminishes proteoglycan loiss in human OA cartilage: donor-specific link between IL-37 and MMP-3.
OBJECTIVE:
A hallmark of osteoarthritis (OA) is degradation of articular cartilage proteoglycans. In isolated human OA chondrocytes, the anti-inflammatory cytokine Interleukin-37 (IL-37) lowers the expression of the proteolytic MMP and ADAMTS enzymes, which mediate this degradation. Therefore, we i…
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Journal:
Authors:
- Van Geffen EW,
- Van Caam APM,
- Van de Loo FA,
- Van Lent PLEM,
- Koenders MI,
- Thudium CS,
- Bay-Jensen AC,
- Blaney Davidson EN,
- Van der Kraan PM,
Hepatic System
5. Sep 2018
No effect of rifaximin on soluble CD163, mannose receptor of type III and IV neoepitope collagen markers in decompensated cirrhosis: Results from a randomized placebo controlled trial
BACKGROUND AND AIMS:
Macrophages play a significant role in chronic liver disease as reflected by elevated soluble (s)CD163 and mannose receptor (sMR) levels and associated with liver disease severity and prognosis. Extracellular matrix remodelling associated with fibrogenesis may be affected by sy…
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Journal:
Authors:
- kimer N,
- Gudmann NS,
- Pedersen JS,
- Møller S,
- Nielsen MJ,
- Leeming DJ,
- Karsdal MA,
- Møller HJ,
- Bedtsen F,
- Grønbæk H,
Hepatic System
5. Sep 2018
No effect of rifaximin on soluble CD163, mannose receptor or type III and IV neoepitope collagen markers in decompensated cirrhosis: Results from a randomized, placebo controlled trial.
BACKGROUND AND AIMS:
Macrophages play a significant role in chronic liver disease as reflected by elevated soluble (s)CD163 and mannose receptor (sMR) levels and associated with liver disease severity and prognosis. Extracellular matrix remodelling associated with fibrogenesis may be affected by sy…
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Journal:
Authors:
- kimer N,
- Gudmann NS,
- Pedersen JS,
- Møller S,
- Nielsen MJ,
- Leeming DJ,
- Karsdal MA,
- Møller HJ,
- Bendtsen F,
- Grønbæk H,
Hepatic System, Hepatitis B/C
3. Sep 2018
A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic hepatitis B.
BACKGROUND:
Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with…
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Journal:
Authors:
- El Sharkawy R,
- Thabet K,
- Lampertico P,
- Petta S,
- Mangia A,
- Berg T,
- Netwally M,
- Bayoumi A,
- Boonstra A,
- Brouwer WP,
- Smedile A,
- Abate ML,
- Loglio A,
- Douglas MW,
- Khan A,
- Santoro R,
- Fischer J,
- Leeming DJ,
- Liddle C,
- George J,
- Eslam M,
Hepatic System
30. Aug 2018
Assessment of liver fibrosis progresion and regression by a serological collagen turnover profile
OBJECTIVE:
There is a need for non-invasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to anti-fibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be inc…
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Authors:
- Karsdal MA,
- Hjuler ST,
- Luo Y,
- Rasmussen DG,
- Nielsen MJ,
- Nielsen SH,
- Leeming DJ,
- Goodman ZD,
- Arch RH,
- Patel K,
- Schuppan D,
Hepatitis B/C, Hepatic System
30. Aug 2018
Assessment of Liver Fibrosis Progression and Regression by a Serological Collagen Turnover Profile.
OBJECTIVE:
There is a need for non-invasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to anti-fibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be inc…
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Authors:
- Karsdal MA,
- Hjuler ST,
- Luo Y,
- Rasmussen DG,
- Nielsen MJ,
- Holm Nielsen S,
- Leeming DJ,
- goodman Z,
- Arch RH,
- Patel K,
- Schuppan D,
Cardiovascular System, Atherosclerosis, Extracellular Matrix Research, Biomarker position
28. Aug 2018
A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis.
OBJECTIVE:
Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix (ECM) proteins in the arterial wall. Collagen type I (COL1), a component of the arterial ECM, is cleaved by matrix metalloproteinases (MMPs) and known to be remodelled in atherosclerosis. We explor…
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Journal:
Authors:
- Holm Nielsen S,
- Tengryd C,
- Edsfeldt A,
- Genovese F,
- Bengtsson E,
- Karsdal MA,
- Leeming DJ,
- Nilsson J,
- Goncalves I,
Lung, Respiratory System, Oncology
1. Aug 2018
A fragment of SPARC reflecting increased collagen affinity shows pathological relevance in lung cancer - implications of a new collagen chaperone function of SPARC
The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) is known to bind collagens and regulate fibrillogenesis. Cleavage of SPARC at a single peptide bond, increases the affinity for collagens up to 20-fold. To investigate if this specific cleavage has pathological relevance…
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Journal:
Authors:
- Kehlet SN,
- Manon-Jensen T,
- Sun S,
- Brix S,
- Karsdal MA,
- Leeming DJ,
- Willumsen N,
Rheumatology, Osteoarthritis
29. Jul 2018
Tofacitinib and TPCA-1 Exert Chondroprotective Effects on Extracellular Matrix Turnover in Bovine Articular Cartilage Ex vivo.
OBJECTIVE:
Currently, there are no disease-modifying osteoarthritis drugs (DMOADs) approved for osteoarthritis. It is hypothesized that a subtype of OA may be driven by inflammation and may benefit from treatment with anti-inflammatory small molecule inhibitors adopted from treatments of rheumatoid…
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Journal:
Authors:
- Kjelgaard-Petersen CF,
- Sharma N,
- Kayed A,
- Karsdal MA,
- Mobasheri A,
- Hägglund P,
- Bay-Jensen AC,
- Thudium CS,
Oncology, Colorectal, Gastrointestinal, Inflammatory Bowel Disease
20. Jul 2018
Serum type XVI collagen is associated with colorectal cancer and ulcerative colitis indicating a pathological role in gastrointestinal disorders
Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have bioma…
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Journal:
Authors:
- Jensen C,
- Nielsen SH,
- Mortensen JH,
- Kjeldsen J,
- Klinge LG,
- Harling H,
- Jørgensen LN,
- Karsdal MA,
- Willumsen N,
- Leeming DJ,
Hepatic System
16. Jul 2018
Serological markers of extracellular matrix remodeling predict transplant-free survival in primary sclerosing cholangitis
BACKGROUND:
Primary sclerosing cholangitis is a progressive liver disease with a remarkably variable course. Biomarkers of disease activity or prognostic models predicting outcome at an individual level are currently not established.
AIM:
To evaluate the prognostic utility of four biomarkers of…
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Authors:
- Nielsen MJ,
- Thorburn D,
- Leeming DJ,
- Hov JR,
- Nygård S,
- Moum B,
- Saffioti F,
- Gilja OH,
- Boberg KM,
- Mazza G,
- Røsjø H,
- Pinzani M,
- Karlsen TH,
- Karsdal MA,
- Vesterhus M,
Non-Alcoholic Fatty Liver Disease, Hepatic System
16. Jul 2018
ADAPT: An algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis.
BACKGROUND AND AIM:
Given the high global prevalence of non-alcoholic fatty liver disease (NAFLD), the need for relevant non-invasive biomarkers and algorithms to accurately stage disease severity is a critical unmet medical need. Identifying those with advanced fibrosis (≥F3) is the most crucial, …
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Journal:
Authors:
- Daniels SJ,
- Leeming DJ,
- Eslam M,
- Hashem AM,
- Nielsen MJ,
- Krag A,
- Karsdal MA,
- Grove JI,
- Guha IN,
- Kawaguchi T,
- Torimura T,
- McLeod D,
- Akiba J,
- Kaye P,
- de Boer B,
- Aithal GP,
- Adams LA,
- George J,
Bone, Extracellular Matrix Research, Biomarker position
14. Jul 2018
Bone and soft tissue turnover in relation to all-cause mortality in postmenopausal women.
BACKGROUND:
The relationship between levels of extracellular matrix (ECM) turnover and mortality is currently unknown. The study aimed to determine if levels of ECM turnover are predictors of all-cause mortality in a large cohort of post-menopausal women.
METHODS:
5,855 postmenopausal Danish wo…
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Journal:
Authors:
- Bager CL,
- Willumsen N,
- Bay-Jensen AC,
- Nielsen HB,
- Karsdal MA,
Oncology, Breast
20. Jun 2018
High turnover of extracellular matrix reflected by specific protein fragments measured in serum is associated with poor outcomes in two metastatic breast cancer cohorts.
Increased extracellular matrix (ECM) formation and matrix metalloprotease (MMP)-mediated ECM degradation are parts of tumorgenesis and generates collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in serum with outcomes in two i…
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Authors:
- Lipton A,
- Leitzel K,
- Polimera HV,
- Ali SM,
- Naggabhairu V,
- Marks E,
- Richardson AE,
- Krecko L,
- Ali A,
- Koestler W,
- Esteva FJ,
- Leeming DJ,
- Karsdal MA,
- Willumsen N,
Rheumatology, Spondyloarthropathies
14. May 2018
Is radiographic progression in radiographic axial spondyloarthritis related to matrix metalloproteinase degradation of extracellular matrix?
BACKGROUND:
Radiographic axial spondyloarthritis (r-axSpA) is associated with extracellular matrix (ECM) remodelling of affected tissues. We investigated whether there was a relationship between biomarkers of ECM remodelling and 2-year radiographic progression in r-axSpA.
METHODS:
Patients from…
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Journal:
Authors:
- Siebuhr AS,
- van de Heijde D,
- Bay-Jensen AC,
- Karsdal MA,
- Landewé R,
- van Tubergen A,
- Ramiro S,
Rheumatology, Rheumatoid Arthritis
8. May 2018
Type IV collagen metabolism is associated with disease activity, radiographic progression and response to tocilizumab in rheumatoid arthritis
OBJECTIVES:
The expanding spectrum of targeted therapies for rheumatoid arthritis (RA) implies a need for development of precision tools for disease assessment reflecting pathobiologic processes. Type IV collagen is an abundant protein of basement membranes, but is also present in the intercellular…
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Journal:
Authors:
- Gudmann NS,
- Junker P,
- Juhl P,
- Thudium CS,
- Siebuhr AS,
- Byrjalsen I,
- Karsdal MA,
- Bay-Jensen AC,
Respiratory System, Extracellular Matrix Research
4. May 2018
A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia
BACKGROUND:
Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exa…
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Journal:
Authors:
- Sand JMB,
- Tanino Y,
- Karsdal MA,
- Nikaido T,
- Misa K,
- Sato Y,
- Togawa R,
- Wang X,
- Leeming DJ,
- Munakata M,
Rheumatology, Osteoarthritis
25. Apr 2018
Protein biomarkers associated with pain mechanisms in osteoarthritis
Osteoarthritis (OA) is the most common arthritic disease in the world, leading to debilitating pain and destruction of joint tissues. While pain is the hallmark symptom of osteoarthritis, clear associations between pain and disease processes involved in joint deterioration are lacking. OA pain is mu…
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Journal:
Authors:
- Thudium CS,
- Löfvall H,
- Karsdal MA,
- Bay-Jensen AC,
- Bihlet A,
Rheumatology, Osteoarthritis, Extracellular Matrix Research
25. Apr 2018
Aggrecanase degradation of type III collagen is associated with clinical knee pain
There is a lack of biochemical markers for non-invasive and objective assessment of symptomatic osteoarthritis (OA). Aggrecanase activity has been shown to be associated with joint deterioration and symptomatic disease through the degradation of extracellular matrix proteins, such as type III collag…
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Journal:
Authors:
- Bay-Jensen AC,
- Kjelgaard-Petersen CF,
- Petersen KK,
- Arendt-Nielsen L,
- Quasnichka HL,
- Mobasheri A,
- Karsdal MA,
- Leeming DJ,
Rheumatology, Rheumatoid Arthritis
18. Apr 2018
Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis
OBJECTIVE:
Rheumatoid arthritis (RA) is a chronic, autoimmune and degenerative joint disease leading to disability, reduced life quality, and increased mortality. Although several synthetic and biological disease modifying anti-rheumatic drugs (DMARDs) are available, there is still a medical need f…
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Journal:
Authors:
- Kjelgaard-Petersen CF,
- Platt A,
- Braddock M,
- Jenkins MA,
- Musa K,
- Graham E,
- Gantzel T,
- Slynn G,
- Weinblatt ME,
- Karsdal MA,
- Thudium CS,
- Bay-Jensen AC,
Extracellular Matrix Research
13. Apr 2018
Mass spectrometry-based identification of cross-links in proteins exposed to photo-oxidation and peroxyl radicals using 18/O labeling and optimized MS/MS fragmentation
Protein cross-links are formed in regulated biochemical processes in many biological systems, but they are also generated inadvertently via the reactions of exogenous or endogenous oxidants. Site-specific identification and characterization of such cross-links is challenging and the goal was therefo…
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Journal:
Authors:
- Mariotti M,
- Leinisch F,
- Leeming DJ,
- Svensson B,
- Davies MJ,
- Hägglund P,
Central Nervous System, Alzheimer’s Disease
11. Apr 2018
Two novel blood-based biomarker candidates measuring degradation of tau are associated with dementia: a prospective study
BACKGROUND:
Truncated tau appears to be specifically related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer's disease (AD); however, the relevance of truncated Tau measurements in…
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Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Karsdal MA,
- Brix S,
- Henriksen K,
Type 2-Diabetes, Endocrinology, Extracellular Matrix Research
11. Apr 2018
Higher collagen VI formation is associated with all-cause mortality in type 2 diabetic patients with microalbuminuria
OBJECTIVE:
Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI fo…
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Journal:
Authors:
- Rasmussen DGK,
- Hansen TW,
- von Scholten BJ,
- Nielsen SH,
- Reinhard H,
- Parving HH,
- Tepel M,
- Karsdal MA,
- Jacobsen PK,
- Genovese F,
- Rossing P,
Bone, Extracellular Matrix Research, Osteoarthritis
10. Apr 2018
Osteoclasts degrade bone and cartilage knee joint compartments through different resorption processes
BACKGROUND:
Osteoclasts have been strongly implicated in osteoarthritic cartilage degradation, at least indirectly via bone resorption, and have been shown to degrade cartilage in vitro. The osteoclast resorption processes required to degrade subchondral bone and cartilage-the remodeling of which i…
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Journal:
Authors:
- Löfvall H,
- Newbould H,
- Karsdal MA,
- Dziegiel MH,
- Richter J,
- Henriksen K,
- Thudium CS,
Gastrointestinal, Hernia, Extracellular Matrix Research
1. Apr 2018
Type V collagen is persistently altered after inguinal hernia repair
BACKGROUND AND AIMS:
Hernia formation is associated with alterations of collagen metabolism. Collagen synthesis and degradation cause a systemic release of products, which are measurable in serum. Recently, we reported changes in type V and IV collagen metabolisms in patients with inguinal and inci…
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Journal:
Authors:
- Lorentzen L,
- Henriksen NA,
- Juhl P,
- Mortensen JH,
- Ågren MS,
- Karsdal MA,
- Jorgensen LN,
Extracellular Matrix Research, Atherosclerosis
31. Mar 2018
Assessment of extracellular matrix-related biomarkers in patients with lower extremity artery disease
BACKGROUND:
The prevalence of lower extremity artery disease (LEAD) is high (20%-25%) in the population older than 65 years, but patients are seldom identified until the disease is advanced. Circulating markers of disease activity might provide patients with a key opportunity for timely treatment. …
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Journal:
Authors:
- Hernández-Aguilera A,
- Nielsen SH,
- Bonache C,
- Fernández-Arroyo S,
- Martín-Paredero V,
- Fibla M,
- Karsdal MA,
- Genovese F,
- Menendez JA,
- Camps J,
- Joven J,
Extracellular Matrix Research
29. Mar 2018
Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix
The extracellular matrix (ECM) plays a vital role in maintaining normal tissue function. Collagens are major components of the ECM and there is a tight equilibrium between degradation and formation of these proteins ensuring tissue health and homeostasis. As a consequence of tissue turnover, small c…
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Journal:
Authors:
- Kehlet SN,
- Willumsen N,
- Armbrecht G,
- Dietzel R,
- Brix S,
- Henriksen K,
- Karsdal MA,
Extracellular Matrix Research
29. Mar 2018
Matrix Metalloproteinase Mediated Type I Collagen Degradation is an Independent Predictor of Increased Risk of Acute Myocardial Infarction in Postmenopausal Women
Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major r…
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Journal:
Authors:
- Bertelsen DM,
- Neergaard JS,
- Bager CL,
- Nielsen SH,
- Secher NH,
- Svendsen JH,
- Bihlet AR,
- Andersen JR,
- Karsdal MA,
- Christiansen C,
- Nielsen HB,
Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis, Lung, Extracellular Matrix Research
7. Mar 2018
Tumstatin, a Matrikine Derived from Collagen Type IVα3, is Elevated in Serum from Patients with Non-Small Cell Lung Cancer
OBJECTIVES
Fibrosis and cancer are characterized by extracellular matrix (ECM) remodeling. The basement membrane is mainly composed by collagen type IV and laminin. Tumstatin is a matrix metalloproteinase-9 (MMP-9) generated matrikine of collagen type IV α3 chain. We evaluated the potential of tums…
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Journal:
Authors:
- Nielsen SH,
- Willumsen N,
- Brix S,
- Sun S,
- Manon-Jensen T,
- Karsdal MA,
- Genovese F,
Extracellular Matrix Research, Systemic Sclerosis, Rheumatology, Chronic Obstructive Pulmonary Disease
1. Mar 2018
Development of a Neo-Epitope Specific Assay for Serological Assessment of Type VII Collagen Turnover and Its Relevance in Fibroproliferative Disorders
Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients wi…
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Journal:
Authors:
- Sand JMB,
- Lamy P,
- Juhl P,
- Siebuhr AS,
- Iversen LV,
- Nawrocki A,
- Larsen MR,
- Domsic RT,
- Franchimont N,
- Chavez J,
- Karsdal MA,
- Leeming DJ,
Rheumatology, Rheumatoid Arthritis
14. Feb 2018
Increased remodelling of interstitial collagens and basement membrane is suppressed by treatment in patients with rheumatoid arthritis: serological evaluation of a one-year prospective study of 149 Japanese patients
OBJECTIVES:
This prospective study aimed to use serological biomarkers for evaluation of, connective tissue turnover, in a population of 149 Japanese patients with rheumatoid arthritis (RA). It was aimed to investigate how the connective tissue was affected by treatment at follow-up after 1 year (+…
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Journal:
Authors:
- Gudmann NS,
- Hirata S,
- Karsdal MA,
- Kubo S,
- Bay-Jensen AC,
- Tanaka Y,
Rheumatology, Rheumatoid Arthritis
31. Jan 2018
IL-6 receptor inhibition modulates type III collagen and C-reactive protein degradation in rheumatoid arthritis patients with an inadequate response to anti-tumour necrosis factor therapy: analysis of connective tissue turnover in the tocilizumab RADIATE.
OBJECTIVES:
The objective of this study was to examine the tissue degradation in response to anti-IL6 receptor treatment in rheumatoid arthritis (RA) patients which are anti-TNF-α inadequate responders.
METHODS:
RADIATE was a randomised, double-blinded, placebo-controlled, parallel-group, phase…
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Journal:
Authors:
- Juhl P,
- Thudium CS,
- Gudmann NS,
- Karsdal MA,
- Bay-Jensen AC,
- Siebuhr AS,
Hepatic System
18. Jan 2018
Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis
Patients with end-stage liver disease develop acute decompensation (AD) episodes, which become more frequent and might develop into acute-on-chronic liver failure (ACLF). However, it remains unknown how AD induces acceleration of liver disease. We hypothesized that remodeling of collagen type III pl…
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Journal:
Authors:
- Praktiknjo M,
- Lehmann J,
- Nielsen MJ,
- Schierwagen R,
- Uschner FE,
- Meyer C,
- Thomas D,
- Strassburg CP,
- Bendtsen F,
- Møller S,
- Krag A,
- Karsdal MA,
- Leeming DJ,
- Trebicka J,
Osteoarthritis
17. Jan 2018
Identification of pain categories associated with change in pain in patients receiving placebo: Data from Two Phase 3 Randomized Clinical Trials in Symptomatic Knee Osteoarthritis
BACKGROUND:
Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describing clinica…
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Journal:
Authors:
- Bihlet AR,
- Byrjalsen I,
- Bay-Jensen AC,
- Andersen JR,
- Christiansen C,
- Riis BJ,
- Valter I,
- Karsdal MA,
- Hochberg MC,
Hematology, Hemophilia
10. Jan 2018
The endothelial specific isoform of type XVIII collagen correlates to annual bleeding rate in haemophilia patients
INTRODUCTION:
The medical need in the haemophilic (HF) field to reduce bleeding incidents requires measurement of the annual bleeding rate (ABR) in haemophiliacs. Vascular rupture is associated with damage to the vascular endothelium causing exposure of the basement membrane. Endothelial cells and …
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Journal:
Authors:
- Kjeld NG,
- Hua B,
- Karsdal MA,
- Sun S,
- Manon-Jensen T,
Rheumatology, Osteoarthritis, Clinical Data Quality
9. Jan 2018
Gender Differences in Knee Joint Congruity Quantified from MRI: A Validation Study with Data from Center for Clinical and Basic Research and Osteoarthritis Initiative.
Objective Gender is a risk factor in the onset of osteoarthritis (OA). The aim of the study was to investigate gender differences in contact area (CA) and congruity index (CI) in the medial tibiofemoral (MTF) joint in 2 different cohorts, quantified automatically from magnetic resonance imaging (MRI…
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Journal:
Authors:
- Tummala S,
- Schipdor D,
- Byrjalsen I,
- Dam EB,
Cardiovascular System, Extracellular Matrix Research, Myocardial Fibrosis
1. Jan 2018
Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy
AIM:
Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patie…
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Journal:
Authors:
- Nielsen SH,
- Mygind ND,
- Michelsen MM,
- Bechsgaard DF,
- Suhrs HE,
- Genovese F,
- Nielsen HB,
- Brix S,
- Karsdal MA,
- Prescott E,
- Kastrup J,
Cardiovascular System, Extracellular Matrix Research
14. Dec 2017
Understanding Cardiac Extracellular Matrix Remodeling to Develop Biomarkers of Myocardial Infarction Outcomes
Cardiovascular Disease (CVD) is the most common cause of death in industrialized countries, and myocardial infarction (MI) is a major CVD with significant morbidity and mortality. Following MI, the left ventricle (LV) undergoes a wound healing response to ischemia that results in extracellular matri…
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Journal:
Authors:
- Nielsen SH,
- Mouton AJ,
- DeLeon-Pennell KY,
- Genovese F,
- Karsdal MA,
- Lindsey ML,
Rheumatology, Osteoarthritis
12. Dec 2017
Sprifermin (rhFGF18) Modulates Extracellular Matrix Turnover in Cartilage Explants ex vivo
BACKGROUND:
Sprifermin (recombinant human fibroblast growth factor 18) is in clinical development as a potential disease-modifying osteoarthritis drug (DMOAD). In vitro studies have shown that cartilage regenerative properties of sprifermin involve chondrocyte proliferation and extracellular matrix…
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Journal:
Authors:
- Reker D,
- Kjelgaard-Petersen CF,
- Siebuhr AS,
- Michaelis M,
- Gigout A,
- Karsdal MA,
- Ladel C,
- Bay-Jensen AC,
Renal System, Chronic Renal Disease
11. Dec 2017
Urinary endotrophin predicts disease progression in patients with chronic kidney disease
Renal fibrosis is the central pathogenic process in progression of chronic kidney disease (CKD). Collagen type VI (COL VI) is upregulated in renal fibrosis. Endotrophin is released from COL VI and promotes pleiotropic pro-fibrotic effects. Kidney disease severity varies considerably and accurate inf…
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Journal:
Authors:
- Rasmussen DG,
- Fenton A,
- Jesky M,
- Ferro C,
- Boor P,
- Tepel M,
- Karsdal MA,
- Genovese F,
- Cockwell P,
Chronic Obstructive Pulmonary Disease, Respiratory System
4. Dec 2017
Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study
BACKGROUND:
Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1.
METHODS:
One thousand COPD subjects from the observatio…
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Journal:
Authors:
- Leeming DJ,
- Byrjalsen I,
- Sand JMB,
- Bihlet AR,
- Lange P,
- Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators,
- Thal-Singer R,
- Miller BE,
- Karsdal MA,
- Vestbo J,
Extracellular Matrix Research
1. Dec 2017
Objective Cognitive Impairment and Progression to Dementia in Women: The Prospective Epidemiological Risk Factor Study.
BACKGROUND:
Identification of subjects with a progressive disease phenotype is an urgent need in the pharmaceutical industry where most of the recent clinical trials in Alzheimer's disease have failed.
OBJECTIVES:
The objective of this study was to identify subgroups of individuals with objecti…
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Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Karsdal MA,
- Brix S,
- Henriksen K,
Hepatic System, Extracellular Matrix Research
6. Nov 2017
Inducible knockdown of procollagen I protects mice from liver fibrosis and leads to dysregulated matrix genes and attenuated inflammation
Organ fibrosis is characterized by a chronic wound-healing response, with excess deposition of extracellular matrix components. Here, collagen type I represents the most abundant scar component and a primary target for antifibrotic therapies. Liver fibrosis can progress to cirrhosis and primary live…
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Journal:
Authors:
- Molokanova O,
- Schönig K,
- Weng SY,
- Wang X,
- Bros M,
- Diken M,
- Ohngemach S,
- Karsdal MA,
- Strand D,
- Nikolaev A,
- Eshkind L,
- Schuppan D,
Gastrointestinal, Hepatitis B/C, Hepatic System
25. Oct 2017
PRO-C3: a new and more precise collagen marker for liver fibrosis in patients with chronic hepatitis C
OBJECTIVE:
Detecting significant fibrosis and cirrhosis remains important in treatment and follow-up of patients with chronic hepatitis C Infection (CHC). The aim of this study was to assess the ability of PRO-C3 to identify significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5) both …
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Journal:
Authors:
- Hansen JF,
- Juul Nielsen M,
- Nyström K,
- Leeming DJ,
- Lagging M,
- Norkrans G,
- Brehm Christensen P,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
23. Oct 2017
Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell activities in rheumatoid arthritis
OBJECTIVES:
Targeting the granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway holds great potential in the treatment of inflammatory diseases. Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody, has demonstrated clinical efficacy in RA. Our current study aimed to elucidate me…
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Journal:
Authors:
- Guo X,
- Higgs BW,
- Bay-Jensen AC,
- Wu Y,
- Karsdal MA,
- Kuziora M,
- Godwood A,
- Close D,
- Ryan PC,
- Roskos LK,
- White WI,
Rheumatology, Osteoarthritis
16. Oct 2017
Development and use of biochemical markers in osteoarthritis: current update
PURPOSE OF REVIEW:
There is an increasing demand for noninvasive and descriptive biochemical markers (biomarkers) in osteoarthritis; for enabling early drug development (including translational research), evaluating clinical trial at an early stage and for subtyping. Purpose of the review is to rev…
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Journal:
Authors:
- Bay-Jensen AC,
- Thudium CS,
- Mobasheri A,
Rheumatology, Osteoarthritis
14. Oct 2017
Biochemical marker discovery, testing and evaluation for facilitating OA drug discovery and development
Osteoarthritis (OA) is the most common form of joint disease. This presents the OA research community and pharmaceutical companies developing disease-modifying OA drugs (DMOADs) with great opportunities. The different OA subtypes complicate the traditional approaches for developing new treatments. I…
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Journal:
Authors:
- Bay-Jensen AC,
- Thudium CS,
- Mobasheri A,
- Gualillo O,
Gastrointestinal, Extracellular Matrix Research, Inflammatory Bowel Disease
13. Oct 2017
Ulcerative colitis, Crohn's disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn's disease
BACKGROUND:
Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD). However, the differences in extracellular matrix remodelling (ECM) in Crohn's disease (CD) and ulcerative colitis (UC) are not well described. An increased understanding of the inflammatory pr…
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Journal:
Authors:
- Bay-Jensen AC,
- Karsdal MA,
- Krag A,
- Kjeldsen J,
- Klinge LG,
- Hägglund P,
- Jensen MD,
- Manon-Jensen T,
- Mortensen JH,
Oncology, Extracellular Matrix Research
11. Oct 2017
Quantification of altered tissue turnover in a liquid biopsy: a proposed precision medicine tool to assess chronic inflammation and desmoplasia associated with a pro-cancerous niche and response to immuno-therapeutic anti-tumor modalities
Immuno-therapy has begun to revolutionize cancer treatment. However, despite the significant progress achieved in regard to the duration of clinical benefits, a substantial number of patients do not respond to these therapies. To improve the outcome of patients receiving immuno-therapy, there is a n…
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Journal:
Authors:
- Willumsen N,
- Thomsen LB,
- Bager CL,
- Jensen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
28. Sep 2017
Safety, Tolerability, and Pharmacodynamics of an Anti-Interleukin-1 α/β Dual Variable Domain Immunoglobulin in Patients With Osteoarthritis of the Knee: A Randomized Phase 1 Study
OBJECTIVE:
To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1β, in patients with knee osteoarthritis (OA).
METHOD:
This was a randomized, double-blind, plac…
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Journal:
Authors:
- Wang SX,
- Abramson SB,
- Attur M,
- Karsdal MA,
- Preston RA,
- Lozada CJ,
- Kosloski MP,
- Hong F,
- Jiang P,
- Saltarelli MJ,
- Hendrickson BA,
- Medema JK,
Rheumatology, Osteoarthritis
16. Sep 2017
Biomarkers for equine joint injury and osteoarthritis
We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bon…
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Journal:
Authors:
- McIlwraith CW,
- Kawcak CE,
- Frisbie DD,
- Little CB,
- Clegg PD,
- Peffers MJ,
- Karsdal MA,
- Ekman S,
- Laverty S,
- Slayden RA,
- Sandell LJ,
- Lohmander LS,
- Kraus VB,
Rheumatology, Osteoarthritis, Obesity
9. Sep 2017
A machine learning approach for the identification of new biomarkers for knee osteoarthritis development in overweight and obese women
OBJECTIVE:
Knee osteoarthritis (OA) is among the higher contributors to global disability. Despite its high prevalence, currently, there is no cure for this disease. Furthermore, the available diagnostic approaches have large precision errors and low sensitivity. Therefore, there is a need for new …
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Journal:
Authors:
- Bacardit J,
- Henrotin Y,
- Bierma-Zeinstra SMA,
- Thudium CS,
- Bay-Jensen AC,
- Runhaar J,
- Lazzarini N,
Cardiovascular System, Central Nervous System
5. Sep 2017
The Gly16 Allele of the G16R Single Nucleotide Polymorphism in the β2 -Adrenergic Receptor Gene Augments the Glycemic Response to Adrenaline in Humans
Cerebral non-oxidative carbohydrate consumption may be driven by a β2-adrenergic mechanism. This study tested whether the 46G A (G16R) single nucleotide polymorphism of the β2-adrenergic receptor gene (ADRB2) influences the metabolic and cerebrovascular responses to administration of adrenaline. Fo…
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Journal:
Authors:
- Rokamp KZ,
- Staalsø JM,
- Zaar M,
- Rasmussen P,
- Petersen LG,
- Nielsen RV,
- Secher NH,
- Olsen NV,
- Nielsen HB,
Rheumatology, Extracellular Matrix Research
30. Aug 2017
Changes of patient-reported outcomes and protein fingerprint biomarkers after exercise therapy for axial spondyloarthritis
The objective of this study was to investigate the patient-reported outcomes (PROs) and matrix metalloproteinase (MMP) derived extracellular matrix (ECM) biomarkers in non-radiographic (nr)-axial spondyloarthritis (axSpA) and radiographic (r)-axSpA after exercise intervention. Forty-six axSpA patien…
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Journal:
Authors:
- Husakova M,
- Siebuhr AS,
- Pavelka K,
- Spiritovic M,
- Bay-Jensen AC,
- Levitova A,
Hematology, Hemophilia
29. Aug 2017
Increased basement membrane turnover and strongly attenuated interstitial matrix turnover is a key pathological feature of haemophilia
Altered extracellular matrix (ECM) turnover is a central pathological feature of many diseases. The ECM is a meshwork of molecules that provides structural support to cells throughout the body. It consists mainly of two membranes: the interstitial matrix, which is present between parenchymal cells i…
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Journal:
Authors:
- Manon-Jensen T,
- Hua BL,
- Olsen EHN,
- Sun S,
- Gudme CN,
- Li J,
- Lei W,
- Vandahl B,
- Roepstorff K,
- Kjelgaard-Hansen M,
- Zhao Y,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
28. Aug 2017
Suppression of active, but not total MMP-3, is associated with treatment response in a phase III clinical study of rheumatoid arthritis
OBJECTIVE:
Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a com…
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Journal:
Authors:
- Siebuhr AS,
- Kjelgaard-Petersen CF,
- Sun S,
- Byrjalsen I,
- Christiansen C,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
18. Aug 2017
Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix
OBJECTIVE:
Fibroblast growth factor (FGF) 18 has been shown to increase cartilage volume when injected intra-articularly in animal models of osteoarthritis (OA) and in patients with knee OA (during clinical development of the recombinant human FGF18, sprifermin). However, the exact nature of this e…
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Journal:
Authors:
- Gigout A,
- Guehring H,
- Froemel D,
- Meurer A,
- Ladel C,
- Reker D,
- Bay-Jensen AC,
- Karsdal MA,
- Lindemann S,
Extracellular Matrix Research, Peripheral Vascular Disease
12. Aug 2017
Non-invasive evaluation of extracellular matrix remodeling in peripheral artery disease
AIM:
Peripheral artery disease (PAD) is a common manifestation of systemic atherosclerosis affecting peripheral arteries. The underlying pathology of PAD are disorganized extracellular matrix (ECM), caused by inflammation and oxidation. Previous studies have demonstrated an important structure dis…
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Journal:
Authors:
- Aguilera AH,
- Nielsen SH,
- Fernández-Arroyo S,
- Martín-Paredero V,
- Karsdal MA,
- Genovese F,
- Camps J,
- Joven J,
Oncology, Lung
9. Aug 2017
Cathepsin-S degraded decorin are elevated in fibrotic lung disorders - development and biological validation of a new serum biomarker
BACKGROUND:
Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue h…
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Journal:
Authors:
- Karsdal MA,
- Leeming DJ,
- Brix S,
- Curran M,
- Brodmerkel C,
- Dasgupta B,
- Willumsen N,
- Bager CL,
- Kehlet SN,
Cardiovascular System
6. Aug 2017
Low vs. high haemoglobin trigger for transfusion in vascular surgery: protocol for a randomised trial
BACKGROUND:
In patients with cardiovascular disease, guidelines for administration of red blood cells (RBC) are mainly based on studies outside the vascular surgical setting with the recommendation to use a haemoglobin (hb) trigger-level lower than by guidelines from The European Society for Vascul…
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Journal:
Authors:
- Shahidi S,
- Hellemann D,
- Pedersen OB,
- Wetterslev J,
- Nielsen HB,
- Møller A,
Obesity, Rheumatology, Osteoarthritis
27. Jul 2017
Effects of dietary weight loss with and without exercise on interstitial matrix turnover and tissue inflammation biomarkers in adults with knee osteoarthritis: the Intensive Diet and Exercise for Arthritis trial (IDEA)
OBJECTIVE:
To examine the effects of dietary weight loss, with and without exercise, on selected soluble biomarkers in overweight and obese older adults with symptomatic knee osteoarthritis (OA).
DESIGN:
Blood samples were analyzed from 429 participants in the Intensive Diet and Exercise for Ar…
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Journal:
Authors:
- Loeser RF,
- Beavers DP,
- Bay-Jensen AC,
- Karsdal MA,
- Nicklas BJ,
- Guermazi A,
- Hunter DJ,
- Messier SP,
Renal System, Type 2-Diabetes, Obesity
26. Jul 2017
High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy
ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates …
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Journal:
Authors:
- Dower K,
- Zhao S,
- Schlerman FJ,
- Savary L,
- Campanholle G,
- Johnson BG,
- Xi L,
- Nguyen V,
- Zhan Y,
- Lech MP,
- Wang J,
- Nie Q,
- Karsdal MA,
- Genovese F,
- Boucher G,
- Brown TP,
- Zhang B,
- Homer BL,
- Martinez RV,
Extracellular Matrix Research
21. Jul 2017
The good and the bad collagens of fibrosis - Their role in signaling and organ function
Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or…
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Journal:
Authors:
- Karsdal MA,
- Nielsen SH,
- Leeming DJ,
- Langholm LL,
- Nielsen MJ,
- Manon-Jensen T,
- Siebuhr AS,
- Gudmann NS,
- Rønnow S,
- Sand JM,
- Daniels SJ,
- Mortensen JH,
- Schuppan D,
Bone, Osteoporosis
20. Jul 2017
Targeting NSG mice-engrafting cells with a clinically applicable lentiviral vector corrects osteoclasts in Infantile Malignant Osteopetrosis
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically…
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Journal:
Authors:
- Moscatelli I,
- Löfvall H,
- Schneider Thudium C,
- Rothe M,
- Montano C,
- Kertész Z,
- Sirin M,
- Schulz A,
- Schambach A,
- Henriksen K,
- Richter J,
Cardiovascular System, Type 2-Diabetes
17. Jul 2017
Is cardiovascular disease in patients with diabetes associated with serum levels of MMP-2, LOX, and the elastin degradation products ELM and ELM-2?
BACKGROUND:
Diabetes mellitus type 2 (T2DM) is a significant risk factor for the development of cardiovascular diseases (CVDs). In a previous microarray study of internal mammary arteries from patients with and without T2DM, we observed several elastin-related genes with altered mRNA-expression in …
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Journal:
Authors:
- Rasmussen LM,
- Leeming DJ,
- Karsdal MA,
- Poulsen MK,
- Christiansen AL,
- Thorsen AF,
- Preil SAR,
Bone
15. Jul 2017
Preventive effects of kudzu root on bone loss and cartilage degradation in ovariectomized rat
The clinical utility of Traditional Chinese Medicine (TCM) herbs/roots extracts in osteoporosis (OP) and osteoarthritis (OA) has been described in multiple reports, but there have been few studies of TCM for preventing bone loss and cartilage degradation simultaneously. Six-month-old female Sprague-…
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Authors:
- Luo Y,
- Zheng S,
- Ding Y,
- Dai Y,
- Zhou Y,
- Xiang R,
- Qvist P,
- Zheng Q,
- Bay-Jensen AC,
- Karsdal MA,
Oncology, Colorectal
13. May 2017
Unique insight into microenvironmental changes in colorectal cancer: Ex vivo assessment of matrix metalloprotease-mediated molecular changes in human colorectal tumor tissue and corresponding non-neoplastic adjacent tissue
Matrix metalloprotease (MMP)-mediated tissue remodeling is one of the malignant changes driving colorectal cancer. Measurement of altered MMP expression/activity is not sufficient to fully understand the effect of MMP-mediated tissue remodeling. Biomarkers are required that specifically reflect the …
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Journal:
Authors:
- Willumsen N,
- Bager CL,
- Bay-Jensen AC,
- Kehlet SN,
- Harling H,
- Leeming DJ,
- Karsdal MA,
- Jorgensen LN,
Central Nervous System, Biomarker position
10. May 2017
Modifiable risk factors promoting neurodegeneration is associated with two novel brain degradation markers measured in serum
There has been limited success with blood-based biomarkers of neurodegeneration. One perceived reason is that blood has no direct contact to the brain. Recently developed blood-based biomarkers of tau-degradation have shown promise as potential tools for peripheral assessment of neurodegeneration; h…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Brix S,
- Workman CT,
- Nielsen HB,
- Christiansen C,
- Dragsbæk K,
- Neergaard JS,
Gastrointestinal, Inflammatory Bowel Disease
8. May 2017
Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease
BACKGROUND:
Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease.
AIM:
To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complication…
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Journal:
Authors:
- Van Haaften WT,
- Mortensen JH,
- Karsdal MA,
- Bay-Jensen AC,
- Dijkstra G,
- Olinga P,
Type 2-Diabetes, Obesity, Endocrinology
24. Apr 2017
The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Works as Adjunct to Metformin on Fasting Hyperglycemia and HbA1c in a Rat Model of Type 2 Diabetes
KBP-042 is a dual amylin and calcitonin receptor agonist that increases glucose tolerance and insulin action and reduces body weight in rat models of obesity and prediabetes. The objective of the present study was to 1) evaluate KBP-042 as a treatment of late-stage type 2 diabetes in a rat model and…
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Journal:
Authors:
- Hjuler ST,
- Gydesen S,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Rheumatology, Hematology, Hemophilia
24. Apr 2017
Serological biomarkers detect active joint destruction and inflammation in patients with haemophilic arthropathy
INTRODUCTION:
Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia.
AIM:
We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophili…
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Journal:
Authors:
- Hua B,
- Olsen EHN,
- Sun S,
- Gudme CN,
- Wang L,
- Vandahl B,
- Roepstorff K,
- Kjelgaard-Hansen M,
- Sørensen BB,
- Zhao Y,
- Karsdal MA,
- Manon-Jensen T,
Renal System, Chronic Renal Disease
21. Apr 2017
Non-invasive quantification of collagen turnover in renal transplant recipients
Kidney allograft failure due to chronic injury/rejection remains the main cause of graft loss in renal transplant recipients (RTR). Here, we investigated whether specific biomarkers of extracellular matrix (ECM) turnover are associated with allograft function and chronic kidney disease (CKD) stage i…
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Journal:
Authors:
- Stribos EGD,
- Nielsen SH,
- Brix S,
- Karsdal MA,
- Seelen MA,
- van Goor H,
- Bakker SJL,
- Olinga P,
- Mutsaers HAM,
- Genovese F,
Chronic Renal Disease, Renal System
12. Apr 2017
Serum endotrophin, a type VI collagen cleavage product, is associated with increased mortality in chronic kidney disease
BACKGROUND:
Patients with chronic kidney disease (CKD) are at increased risk of end-stage renal disease (ESRD) and early mortality. The underlying pathophysiological processes are not entirely understood but may include dysregulation of extracellular matrix formation with accelerated systemic and r…
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Journal:
Authors:
- Genovese F,
- Cockwell P,
- Karsdal MA,
- Sørensen J,
- Ferro CJ,
- Jesky MD,
- Fenton A,
Endocrinology, Type 2-Diabetes
7. Apr 2017
Metabolic Syndrome, Insulin Resistance, and Cognitive Dysfunction: Does Your Metabolic Profile Affect Your Brain?
Dementia and type 2 diabetes are both characterized by long prodromal phases, challenging the study of potential risk factors and their temporal relation. The progressive relation among metabolic syndrome, insulin resistance (IR), and dementia has recently been questioned, wherefore the aim of this …
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Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Nielsen HB,
- Brix S,
- Karsdal MA,
- Henriksen K,
Extracellular Matrix Research, Osteoarthritis
22. Mar 2017
Biomarker of extracellular matrix remodelling C1M and proinflammatory cytokine IL-6 are related to synovitis and pain in endstage knee osteoarthritis patients
Little is known about local and systemic biomarkers in relation to synovitis and pain in end-stage osteoarthritis (OA) patients. We investigated the associations between the novel extracellular matrix biomarker, C1M, and local and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, pla…
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Journal:
Authors:
- Radojcic MR,
- Thudium CS,
- Henriksen K,
- Tan K,
- Karlsten R,
- Dudley A,
- Chessell I,
- Karsdal MA,
- Bay-Jensen AC,
- Arbit E,
- Guermazi A,
Cardiovascular System, Central Nervous System
22. Mar 2017
Muscle oxygen saturation increases during head-up tilt-induced (pre)syncope
AIM:
To evaluate whether muscle vasodilatation plays a role for hypotension developed during central hypovolaemia, muscle oxygenation (Sm O2 ) was examined during (pre)syncope induced by head-up tilt (HUT). Skin blood flow (SkBF) and oxygenation (Sskin O2 ) were determined because evaluation of Sm …
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Journal:
Authors:
- Lund A,
- Sørensen H,
- Jensen TW,
- Niemann MJ,
- Olesen ND,
- Nielsen HB,
- Olsen NV,
- Secher NH,
Chronic Renal Disease
20. Mar 2017
Urinary collagen degradation products as early markers of progressive renal fibrosis
BACKGROUND:
Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic…
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Journal:
Authors:
- Hijmans RS,
- Rasmussen DG,
- Yazdani S,
- Navis G,
- van Goor H,
- Karsdal MA,
- Genovese F,
- van den Born J,
Obesity
14. Mar 2017
Optimization of Tolerability and Efficacy of Dual Amylin and Calcitonin Receptor Agonist, KBP-089, through Dose Escalation and Combination with a GLP-1 Analogue
Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study, we investigated how to optimize tolerability, while maintaining efficacy of KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in HFD rats. KBP-089 …
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Journal:
Authors:
- Gydesen S,
- Andreassen KV,
- Hjuler ST,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
Lung
7. Mar 2017
Nidogen-1 Degraded by Cathepsin S can be Quantified in Serum and is Associated with Non-Small Cell Lung Cancer
Loss of basement membrane (BM) integrity is typically associated with cancer. Nidogen-1 is an essential component of the BM. Nidogen-1 is a substrate for cathepsin-S (CatS) which is released into the tumor microenvironment. Measuring nidogen-1 degraded by CatS may therefore have biomarker potential …
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Journal:
Authors:
- Willumsen N,
- Bager CL,
- Leeming DJ,
- Bay-Jensen AC,
- Karsdal MA,
Type 2-Diabetes
6. Mar 2017
Weight change and risk of hyperglycaemia in elderly women
BACKGROUND:
Hyperglycaemia increases the risk of type 2 diabetes, heart disease and stroke, and is influenced by weight. However, the impact of preceding weight change on blood glycemia levels in late-life is less well understood.
AIM:
We studied the interplay between weight change and risk of …
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Journal:
Authors:
- Dragsbæk K,
- Neergaard JS,
- Christiansen C,
- Karsdal MA,
- Beck-Nielsen H,
- Brix S,
- Henriksen K,
Osteoarthritis, Rheumatology, Extracellular Matrix Research
20. Feb 2017
Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis
The extracellular matrix (ECM) of articular cartilage is comprised of complex networks of proteins and glycoproteins, all of which are expressed by its resident cell, the chondrocyte. Cartilage is a unique tissue given its complexity and ability to resist repeated load and deformation. The mechanism…
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Journal:
Authors:
- Sanchez C,
- Bay-Jensen AC,
- Pap T,
- Dvir-Ginzberg M,
- Quasnichka H,
- Barrett-Jolley R,
- Mobasheri A,
- Henrotin Y,
Rheumatoid Arthritis, Rheumatology, Extracellular Matrix Research
17. Feb 2017
The minor collagens in articular cartilage
Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, es…
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Journal:
Authors:
- Luo Y,
- Sinkeviciute D,
- He Y,
- Karsdal MA,
- Henrotin Y,
- Mobasheri A,
- Önnerfjord P,
- Bay-Jensen AC,
Extracellular Matrix Research, Biomarker position, Oncology
11. Feb 2017
Excessive matrix metalloprotease-mediated degradation of interstitial tissue (type I collagen) independently predicts short-term survival in an observational study of postmenopausal women diagnosed with cancer
Extensive tissue remodeling mediated by matrix metalloproteases (MMPs) is an important part of cancer. The aim of this study was to investigate whether serum biomarkers reflecting MMP-mediated degradation of type I collagen (C1M), type IV collagen (C4M) and citrullinated vimentin (VICM) were predict…
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Journal:
Authors:
- Willumsen N,
- Bager CL,
- Kehlet SN,
- Dragsbaek K,
- Neergaard JS,
- Hansen HB,
- Bay-Jensen AC,
- Leeming DJ,
- Lipton A,
- Christiansen C,
- Karsdal MA,
Osteoporosis
3. Feb 2017
Forced expression of human M-CSF in CD34+ cells promotes monocyte differentiation in vitro and in vivo but blunts osteoclastogenesis in vitro
OBJECTIVES:
Here, we tested the hypothesis that human M-CSF (hM-CSF) overexpressed in cord blood (CB) CD34+ cells would induce differentiation and survival of monocytes and osteoclasts in vitro and in vivo.
METHODS:
Human M-CSF was overexpressed in cord blood CD34+ cells using a lentiviral vect…
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Journal:
Authors:
- Montano Almendras CP,
- Thudium CS,
- Löfvall H,
- Moscatelli I,
- Schambach A,
- Henriksen K,
- Richter J,
Type 2-Diabetes
21. Jan 2017
A novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference
BACKGROUND AND PURPOSE:
Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co-morbidities.
EXPERIMENTAL APPROACH:
The…
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Journal:
Authors:
- Gydesen S,
- Hjuler ST,
- Freving Z,
- Andreassen KV,
- Sonne N,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
Osteoarthritis
20. Jan 2017
Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients
OBJECTIVE:
Establish a biomarker panel associated with all-cause total joint replacement (TJR) through identification of patients with osteoarthritis (OA) who do or do not progress to TJR and investigate effects of nonsteroidal anti-inflammatory drugs (NSAIDs).
DESIGN:
Serum samples from patien…
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Journal:
Authors:
- Arends RH,
- Karsdal MA,
- Verburg KM,
- West CR,
- Bay-Jensen AC,
- Keller DS,
Extracellular Matrix Research
19. Jan 2017
Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD
BACKGROUND:
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elas…
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Journal:
Authors:
- Bihlet AR,
- Karsdal MA,
- Sand JM,
- Leeming DJ,
- Roberts M,
- Bowler R,
- White W,
Rheumatology, Osteoarthritis
16. Jan 2017
Osteoarthritis Year in Review 2016: biomarkers (biochemical markers)
PURPOSE:
The aim of this "Year in Review" article is to summarize and discuss the implications of biochemical marker related articles published between the Osteoarthritis Research Society International (OARSI) 2015 Congress in Seattle and the OARSI 2016 Congress in Amsterdam.
METHODS:
The PubMe…
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Journal:
Authors:
- Mobasheri A,
- Bay-Jensen AC,
- Van Spil WE,
- Larkin J,
- Levesque MC,
Chronic Obstructive Pulmonary Disease
11. Jan 2017
Development of a Novel Enzyme-Linked Immunosorbent Assay Targeting a Neo-Epitope Generated by Cathepsin-Mediated Turnover of Type III Collagen and Its Application in Chronic Obstructive Pulmonary Disease
A high level of extracellular matrix (ECM) turnover characterizes several lung diseases with fibrotic features. Type III collagen is one of the most abundant collagens in lung parenchyma, and cathepsins play a role in lung pathology, being responsible for tissue remodeling. In this study, we explore…
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Journal:
Authors:
Rheumatology
5. Jan 2017
Type I and III collagen turnover is increased in axial spondyloarthritis and psoriatic arthritis. Associations with disease activity and diagnostic capacity
OBJECTIVES:
To investigate the turnover of type I and III collagen by neo-epitope markers in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA).
METHODS:
Patients with PsA (n=101) or axSpA (n=110) and healthy subjects (n=120) were included. Demographic and clinical data…
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Journal:
Authors:
- Gudmann NS,
- Siebuhr AS,
- Christensen AF,
- Ejstrup L,
- Sørensen GL,
- Loft AG,
- Karsdal MA,
- Bay-Jensen AC,
- Munk HL,
- Junker P,
Bone
14. Dec 2016
High throughput, quantitative analysis of human osteoclast differentiation and activity
Osteoclasts are multinuclear cells that degrade bone under both physiological and pathophysiological conditions. Osteoclasts are therefore a major target of osteoporosis therapeutics aimed at preserving bone. Consequently, analytical methods for osteoclast activity are useful for the development of …
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Journal:
Authors:
- Diepenhorst NA,
- Nowell CJ,
- Rueda P,
- Henriksen K,
- Pierce T,
- Cook AE,
- Pastoureau P,
- Sabatini M,
- Charman WN,
- Christopoulos A,
- Summers RJ,
- Sexton PM,
- Langmead CJ,
Central Nervous System, Alzheimer’s Disease
18. Nov 2016
Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patien…
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Journal:
Authors:
- O'Bryant SE,
- Mielke MM,
- Rissman RA,
- Lista S,
- Vanderstichele H,
- Zetterberg H,
- Lewczuk P,
- Posner H,
- Hall J,
- Johnson L,
- Fong YL,
- Luthman J,
- Jeromin A,
- Batrla-Utermann R,
- Villarreal A,
- Britton G,
- Snyder PJ,
- Henriksen K,
- Grammas P,
- Gupta V,
- Martins R,
- Hampel H,
Central Nervous System, Traumatic Brain Injury
15. Nov 2016
Serum tau fragments predict return to play in concussed professional ice hockey players
INTRODUCTION:
The diagnosis of sports-related concussion is mainly based on subjective clinical symptoms and neuropsychological tests. Thus, reliable brain injury biomarkers to assess when it is safe to return to play are highly desirable. The overall objective of this study was to evaluate the uti…
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Journal:
Authors:
- Shahim P,
- Linemann T,
- Inekci D,
- Karsdal MA,
- Blennow K,
- Tegner Y,
- Zetterberg H,
- Henriksen K,
Cardiovascular System, Central Nervous System
15. Nov 2016
Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia
BACKGROUND:
The mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish the…
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Journal:
Authors:
- Bailey DM,
- Rasmussen P,
- Overgaard M,
- Evans KA,
- Bohm AM,
- Seifert T,
- Brassard P,
- Zaar M,
- Nielsen HB,
- Raven PB,
- Secher NH,
Hematology, Hemophilia
28. Oct 2016
Altered collagen turnover in factor VIII-deficient rats with hemophilic arthropathy identifies potential novel serological biomarkers in hemophilia
ESSENTIALS:
Joint bleeding in hemophilia may induce significant remodeling of the extracellular matrix. Biomarkers of collagen turnover were investigated in a F8-/- rat model of hemophilic arthropathy. Biomarkers of cartilage degradation increased significantly during development of arthropathy. B…
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Journal:
Authors:
- Manon-Jensen T,
- Karsdal MA,
- Nielsen LN,
- Kjelgaard-Hansen M,
- Vandahl B,
- Olsen EHN,
- Enoksson M,
- Roepstorff K,
Oncology
26. Oct 2016
Cohort Profile: The Prospective Epidemiological Risk Factor (PERF) study
The world’s population is ageing. In Europe alone, the elderly population over age 65 will double from 88 to 153 million and the fastest growing segment of the population will be those over 80, tripling in number from 24 to 60 million in 2060. Low birth rates and increasing longevity are the key fac…
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Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Kehlet SN,
- Hansen HB,
- Hansen G,
- Byrjalsen I,
- Alexandersen P,
- Lindgren LM,
- Bihlet AR,
- Riis BJ,
- Andersen JR,
- Qvist P,
- Karsdal MA,
- Christiansen C,
Hepatic System, Type 2-Diabetes
20. Oct 2016
Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to anti-fibrotic therapy
There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic tria…
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Authors:
- Karsdal MA,
- Henriksen K,
- Nielsen MJ,
- Byrjalsen I,
- Leeming DJ,
- Gardner SD,
- Goodman ZD,
- Patel K,
- Krag A,
- Christiansen C,
- Schuppan D,
Rheumatology, Osteoarthritis
11. Oct 2016
The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study
OBJECTIVES:
To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA).
METHODS:
Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhance…
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Journal:
Authors:
- Riis RG,
- Gudbergsen H,
- Simonsen O,
- Henriksen M,
- Al-Mashkur N,
- Eld M,
- Petersen KK,
- Kubassova O,
- Bay Jensen AC,
- Damm J,
- Bliddal H,
- Arendt-Nielsen L,
- Boesen MP,
Extracellular Matrix Research, Respiratory System
4. Oct 2016
High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD - results from the ECLIPSE study
BACKGROUND:
There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortali…
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Journal:
Authors:
- Sand JM,
- Leeming DJ,
- Byrjalsen I,
- Bihlet AR,
- Lange P,
- Tal-Singer R,
- Miller BE,
- Karsdal MA,
- Vestbo J,
Hepatic System, Hepatitis B/C, Extracellular Matrix Research
3. Oct 2016
Fibrosis is not just fibrosis - basement membrane modelling and collagen metabolism differs between hepatitis B- and C-induced injury
BACKGROUND:
While morphological patterns differ, the molecular phenotype of liver fibrosis is considered a stereotypical response to chronic liver injury. However, with different cellular triggers and networks regulating fibrosis, the molecular responses of the injured liver may not be identical.
…
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Journal:
Authors:
- Nielsen MJ,
- Karsdal MA,
- Kazankov K,
- Krag A,
- Grønbæk H,
- Leeming DJ,
- Schuppan D,
- George J,
Bone, Osteoporosis
1. Oct 2016
A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D
This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D …
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Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Andersen JR,
- Bihlet AR,
- Russo LA,
- Alexandersen P,
- Valter I,
- Qvist P,
- Lau E,
- Riis BJ,
- Christiansen C,
- Karsdal MA,
- SMC021 investigators,
Type 2-Diabetes
15. Sep 2016
Metabolic syndrome and subsequent risk of type 2 diabetes and cardiovascular disease in elderly women: Challenging the current definition
The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) a…
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Journal:
Authors:
- Dragsbæk K,
- Neergaard JS,
- Laursen JM,
- Hansen HB,
- Christiansen C,
- Beck-Nielsen H,
- Karsdal MA,
- Brix S,
- Henriksen K,
Type 2-Diabetes
8. Sep 2016
Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes
AIMS/HYPOTHESIS:
The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of pro…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Genovese F,
- Leeming DJ,
- Nielsen MJ,
- Riis BJ,
- Christiansen C,
- Byrjalsen I,
- Schuppan D,
Respiratory System, Chronic Obstructive Pulmonary Disease
7. Sep 2016
Characterization of serological neo-epitope biomarkers reflecting collagen remodeling in clinically stable chronic obstructive pulmonary disease
OBJECTIVES:
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been…
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Journal:
Authors:
- Lange P,
- Leeming DJ,
- Karsdal MA,
- Midjord AK,
- Martinez G,
- Sand JM,
Bone
30. Aug 2016
Neo-epitope Peptides as Biomarkers of Disease Progression for Muscular Dystrophies and Other Myopathies
For several decades, serological biomarkers of neuromuscular diseases as dystrophies, myopathies and myositis have been limited to routine clinical biochemistry panels. Gauging the pathological progression is a prerequisite for proper treatment and therefore identifying accessible, easy to monitor b…
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Journal:
Authors:
- Arvanitidis A,
- Henriksen K,
- Karsdal MA,
- Nedergaard AF,
Chronic Obstructive Pulmonary Disease
26. Aug 2016
Systemic Biomarkers of Collagen and Elastin Turnover Are Associated With Clinically Relevant Outcomes in COPD
BACKGROUND:
Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD.
METHODS…
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Journal:
Authors:
- Leeming DJ,
- Kristensen JH,
- Karsdal MA,
- Sand JM,
Bone
19. Aug 2016
Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy
Infantile malignant osteopetrosis (IMO) is a rare, recessive disorder characterized by increased bone mass caused by dysfunctional osteoclasts. The disease is most often caused by mutations in the TCIRG1 gene encoding a subunit of the V-ATPase involved in the osteoclasts capacity to resorb bone. We …
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Journal:
Authors:
- Thudium CS,
- Moscatelli I,
- Löfvall H,
- Kertész Z,
- Montano C,
- Bjurström CF,
- Karsdal MA,
- Schulz AS,
- Richter J,
- Henriksen K,
Bone, Osteoporosis
16. Aug 2016
Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial
IMPORTANCE:
Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.
OBJECTIVE:
To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture i…
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Journal:
Authors:
- Miller PD,
- Hattersley G,
- Riis BJ,
- Williams GC,
- Lau E,
- Russo LA,
- Alexandersen P,
- Zerbini CA,
- Hu MY,
- Harris AG,
- Fitzpatrick LA,
- Cosman F,
- Christiansen C,
Rheumatology, Osteoarthritis
2. Aug 2016
Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future
Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying t…
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Journal:
Authors:
- Karsdal MA,
- Michaelis M,
- Ladel C,
- Siebuhr AS,
- Bihlet AR,
- Andersen JR,
- Guehring H,
- Christiansen C,
- Bay-Jensen AC,
- Kraus VB,
Extracellular Matrix Research
1. Aug 2016
Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling
OBJECTIVES:
Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competiti…
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Journal:
Authors:
- Hansen NU,
- Willumsen N,
- Sand JM,
- Larsen L,
- Karsdal MA,
- Leeming DJ,
Respiratory System
1. Aug 2016
Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF
RATIONALE:
Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberran…
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Journal:
Authors:
- Mercer PF,
- Woodcock HV,
- Eley JD,
- Platé M,
- Sulikowski MG,
- Durrenberger PF,
- Franklin L,
- Nanthakumar CB,
- Man Y2,
- Genovese F,
- McAnulty RJ,
- Yang S,
- Maher TM,
- Nicholson AG,
- Arbit E,
- Marshall RP,
- Lukey PT,
- Chambers RC,
Endocrinology, Type 2-Diabetes
1. Aug 2016
The dual amylin- and calcitonin-receptor agonist KBP-042 increases insulin sensitivity and induces weight loss in rats with obesity
OBJECTIVE:
In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 µg/kg-10 µg/kg) compared with saline-treated and pair-fed controls.
METHODS:
Rats with obesity received daily s.c…
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Journal:
Authors:
- Hjuler ST,
- Gydesen S,
- Andreassen KV,
- Pedersen SL,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
Colorectal
28. Jul 2016
Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients
During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of prote…
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Journal:
Authors:
- Kehlet SN,
- Sanz-Pamplona R,
- Brix S,
- Leeming DJ,
- Karsdal MA,
- Moreno V,
Extracellular Matrix Research
27. Jul 2016
Quantification of fibronectin as a method to assess ex vivo extracellular matrix remodeling
Altered architecture, composition and quality of the extracellular matrix (ECM) are pathological hallmarks of several inflammatory and fibro-proliferative pathological processes such as osteoarthritis (OA), rheumatoid arthritis (RA), fibrosis and cancer. One of the most important components of the E…
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Journal:
Authors:
- Bager CL,
- Gudmann NS,
- Willumsen N,
- Leeming DJ,
- Karsdal MA,
- Bay-Jensen AC,
- Høgdall E,
- Balslev I,
- He Y,
Oncology
13. Jul 2016
Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study
BACKGROUND:
An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded t…
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Journal:
Authors:
- Bager CL,
- Willumsen N,
- Kehlet SN,
- Hansen HB,
- Bay-Jensen AC,
- Leeming DJ,
- Dragsbæk K,
- Neergaard JS,
- Christiansen C,
- Høgdall E,
- Karsdal MA,
Extracellular Matrix Research, Respiratory System
5. Jul 2016
Tissue turnover of collagen type I, III and elastin is elevated in the PCLS model of IPF and can be restored back to vehicle levels using a phosphodiesterase inhibitor
BACKGROUND:
The aim of this study was to develop and validate a model for pulmonary fibrosis, using ex vivo tissue cultures of lungs from bleomycin treated animals, enabling the investigation of fibrosis remodeling using novel biomarkers for the detection of ECM protein fragments. The combination …
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Journal:
Authors:
- Hansen NU,
- Karsdal MA,
- Brockbank S,
- Cruwys S,
- Rønnow S,
- Christiansen C,
Rheumatology
16. Jun 2016
Chondrocyte activity is increased in psoriatic arthritis and axial spondyloarthritis
BACKGROUND:
Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. T…
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Journal:
Authors:
- Gudmann NS,
- Munk HL,
- Christensen AF,
- Ejstrup L,
- Sørensen GL,
- Loft AG,
- Karsdal MA,
- Bay-Jensen AC,
- He Y,
- Siebuhr AS,
- Junker P,
Rheumatology
2. Jun 2016
Intercritical circulating levels of neo-epitopes reflecting matrixmetalloprotease-driven degradation as markers of gout and frequent gout attacks
OBJECTIVE:
Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares.
METHODS:
Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples …
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Journal:
Authors:
- Valdes AM,
- Manon-Jensen T,
- Abhishek A,
- Jenkins W,
- Siebuhr AS,
- Karsdal MA,
- Doherty S,
- Zhang W,
- Richardson H,
- Doherty M,
- Bay-Jensen AC,
Osteoporosis, Bone
1. Jun 2016
Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice
In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery …
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Journal:
Authors:
- Wendelboe MH,
- Thomsen JS,
- Henriksen K,
- Vegger JB,
- Brüel A,
Extracellular Matrix Research, Renal System
22. May 2016
Precision-Cut Kidney Slices as a Tool to Understand the Dynamics of Extracellular Matrix Remodeling in Renal Fibrosis
The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) su…
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Journal:
Authors:
- Genovese F,
- Kàrpàti ZS,
- Nielsen SH,
- Karsdal MA,
Rheumatology, Osteoarthritis
5. May 2016
The Need for Predictive, Prognostic, Objective and Complementary Blood-Based Biomarkers in Osteoarthritis (OA)
Osteoarthritis (OA) has traditionally been viewed as a non-inflammatory arthropathy and has not been considered a ‘serious disease’. However, this view has radically changed in recent years, due to the complexity and heterogeneity of the patient populations, spiralling socio-economical costs and lon…
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Journal:
Authors:
- Bay-Jensen AC,
- Henrotin Y,
- Karsdal MA,
- Mobasheri A,
Endocrinology, Type 2-Diabetes
1. May 2016
KBP-088, a novel DACRA with prolonged receptor activation, is superior to davalintide in terms of efficacy on body weight
This study aims to elucidate the mechanism behind the potent weight loss induced by dual amylin and calcitonin receptor agonists (DACRA) through comparison of the novel DACRA KBP-088 with the amylinomimetic davalintide with regard to in vitro receptor pharmacology and in vivo efficacy on food intake…
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Journal:
Authors:
- Gydesen S,
- Hjuler ST,
- Christensen JM,
- Karsdal MA,
- Arbit E,
- Andreassen KV,
Rheumatology, Osteoarthritis
28. Apr 2016
Osteoarthritis biomarkers derived from cartilage extracellular matrix: Current status and future perspectives
Specific soluble biomarkers can be powerful tools for the diagnosis, prognosis and personalized management of osteoarthritis (OA). Biomarkers are potential indicators of the effect of a drug on cartilage metabolism and provide crucial information about the mechanisms of drug action. In this review, …
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Journal:
Authors:
- Henrotin Y,
- Sanchez C,
- Bay-Jensen AC,
- Mobasheri A,
Gastrointestinal, Hernia
14. Apr 2016
Abdominal wall hernias - A local manifestation of systemically impaired quality of the extracellular matrix
BACKGROUND:
Throughout life, inguinal hernia develops in approximately every fourth man, some of whom develop multiple hernias. If patients at risk of developing multiple hernias could be identified by a serologic biomarker, treatment might be able to be tailored and improved. Evidence suggests tha…
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Journal:
Authors:
- Henriksen NA,
- Mortensen JH,
- Lorentzen L,
- Ågren MS,
- Bay-Jensen AC,
- Jorgensen LN,
- Karsdal MA,
Rheumatology, Osteoarthritis
1. Apr 2016
Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort
BACKGROUND:
We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) i…
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Journal:
Authors:
- Saberi Hosnijeh F,
- Siebuhr AS,
- Uitterlinden AG,
- Oei EH,
- Hofman A,
- Karsdal MA,
- Bierma-Zeinstra SM,
- Bay-Jensen AC,
- van Meurs JB,
Rheumatology, Rheumatoid Arthritis
28. Mar 2016
Neo-Epitopes-Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis
OBJECTIVE:
Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-de…
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Journal:
Authors:
- Maijer KI,
- Gudmann NS,
- Karsdal MA,
- Gerlag DM,
- Tak PP,
- Bay-Jensen AC,
Hemophilia
14. Mar 2016
Collagen-mediated hemostasis
Collagens mediate essential hemostasis by maintaining the integrity and stability of the vascular wall. Imbalanced turnover of collagens by uncontrolled formation and/or degradation may result in pathologic conditions such as fibrosis. Thickening of the vessel wall because of accumulation of collage…
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Journal:
Authors:
- Manon-Jensen T,
- Kjeld NG,
- Karsdal MA,
Alzheimer’s Disease
1. Mar 2016
Late-Life Risk Factors for All-Cause Dementia and Differential Dementia Diagnoses in Women: A Prospective Cohort Study
Since the first evidence of a decline in dementia incidence was reported in 2011, the focus on modifiable risk factors has increased. The possibility of risk factor intervention as a prevention strategy has been widely discussed; however, further evidence in relation to risk factors is still needed.…
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Authors:
Rheumatology, Spondyloarthropathies
10. Feb 2016
CRP and a biomarker of type I collagen degradation, C1M, can differentiate anti-inflammatory treatment response in ankylosing spondylitis
AIM:
To investigate if tissue turnover biomarkers were efficacy biomarkers in ankylosing spondylitis and if the biomarkers at baseline predicted a good outcome (BASDAI50).
PATIENTS & METHODS:
Twenty-two etanercept treated ankylosing spondylitis patients were investigated for inflammation (CRP, …
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Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Karsdal MA,
- Lories RJ,
- de Vlam K,
Rheumatology, Osteoarthritis, Extracellular Matrix Research
10. Feb 2016
Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis
OBJECTIVE:
Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium.
METHODS:
Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in …
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Journal:
Authors:
- Bay-Jensen AC,
- Karsdal MA,
- Ladel C,
- Christiansen TG,
- Siebuhr AS,
- Kjelgaard-Petersen CF,
Renal System
1. Feb 2016
Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease
During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for catheps…
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Journal:
Authors:
- Fox C,
- Cocchiaro P,
- Oakley F,
- Howarth R,
- Callaghan K,
- Leslie J,
- Luli S,
- Wood KM,
- Sheerin NS,
- Genovese F,
- Moles A,
Rheumatology, Osteoarthritis
25. Jan 2016
Osteoarthritis year in review 2015: soluble biomarkers and the BIPED criteria
OBJECTIVE:
To review and summarize biomarker data published from April 2014 to May 2015 to provide insight to the ongoing work in the field of osteoarthritis (OA). Furthermore, to summarize the BIPED criteria and set it in context of the medical needs of 2015.
METHODS:
PubMed was used as search…
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Journal:
Authors:
- Bay-Jensen AC,
- Reker D,
- Kjelgaard-Petersen CF,
- Mobasheri A,
- Karsdal MA,
- Ladel C,
- Henrotin Y,
- Thudium CS,
Rheumatology, Rheumatoid Arthritis
20. Jan 2016
Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study
BACKGROUND:
Rheumatoid arthritis (RA) is characterized by gradual joint destruction. Tocilizumab (TCZ) significantly suppresses symptoms, however not all patients are protected from joint damage. We investigated whether early measurement of specific biomarkers could predict early joint protection r…
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Journal:
Authors:
- Bay-Jensen AC,
- Platt A,
- Siebuhr AS,
- Christiansen C,
- Byrjalsen I,
- Karsdal MA,
Bone, Osteoporosis
6. Jan 2016
Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures
Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, re…
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Journal:
Authors:
- Styrkarsdottir U,
- Thorleifsson G,
- Gudjonsson SA,
- Sigurdsson A,
- Center JR,
- Lee SH,
- Nguyen TV,
- Kwok TC,
- Lee JS,
- Ho SC,
- Woo J,
- Leung PC,
- Kim BJ,
- Rafnar T,
- Kiemeney LA,
- Ingvarsson T,
- Koh JM,
- Tang NL,
- Eisman JA,
- Christiansen C,
- Sigurdsson G,
- Thorsteinsdottir U,
- Stefansson K,
Clinical Data Quality
4. Jan 2016
The impact of clinical trial monitoring approaches on data integrity and cost-a review of current literature
PURPOSE:
Monitoring is a costly requirement when conducting clinical trials. New regulatory guidance encourages the industry to consider alternative monitoring methods to the traditional 100 % source data verification (SDV) approach. The purpose of this literature review is to provide an overview o…
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Authors:
Rheumatology, Osteoarthritis
21. Dec 2015
Serum cartilage oligomeric matrix protein and development of radiographic and painful knee osteoarthritis. A community-based cohort of middle-aged women
CONTEXT AND OBJECTIVE:
We evaluated the predictive value of serum cartilage oligomeric matrix protein (sCOMP) levels over 20 years on the development of radiographic (RKOA) and painful knee osteoarthritis (KOA) in a longitudinal cohort of middle-aged women.
MATERIALS AND METHODS:
Five hundred a…
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Journal:
Authors:
- Kluzek S,
- Bay-Jensen AC,
- Judge A,
- Karsdal MA,
- Shorthose M,
- Spector T,
- Hart D,
- Newton JL,
- Arden NK,
Extracellular Matrix Research
21. Dec 2015
Protein degradation fragments as diagnostic and prognostic biomarkers of connective tissue diseases: understanding the extracellular matrix message and implication for current and future serological biomarkers
The aim of this review is to discuss the potential usefulness of novel biochemical markers of connective tissues: neo-epitopes of extracellular matrix proteins generated by post-translational modifications by tissue proteinases. As each modification results from a specific local physiological or pat…
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Journal:
Authors:
Endocrinology
7. Dec 2015
Collagen Type III and VI Turnover in Response to Long-Term Immobilization
BACKGROUND:
Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarker…
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Journal:
Authors:
- Sun S,
- Henriksen K,
- Karsdal MA,
- Byrjalsen I,
- Rittweger J,
- Armbrecht G,
- Belavý DL,
- Felsenberg D,
- Nedergaard AF,
Endocrinology
6. Dec 2015
Collagen fragment biomarkers as serological biomarkers of lean body mass - a biomarker pilot study from the DAHANCA25B cohort and matched controls
BACKGROUND:
Loss of muscle mass and function is an important complication to ageing and a range of pathologies, including, but not restricted to, cancer, organ failures, and sepsis. A number of interventions have been proposed ranging from exercise to anabolic pharmacological therapy, with varying …
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Journal:
Authors:
- Nedergaard A,
- Dalgas U,
- Primdahl H,
- Johansen J,
- Overgaard J,
- Overgaard K,
- Henriksen K,
- Karsdal MA,
- Lønbro S,
Rheumatology, Osteoarthritis
2. Dec 2015
Sensitization and Serological Biomarkers in Knee Osteoarthritis Patients With Different Degrees of Synovitis
OBJECTIVE:
Synovitis is a frequent condition in knee osteoarthritis (KOA) and has been associated with pain. This study investigated the links between the pressure hyperalgesia, the clinical pain, the degree of the synovitis, inflammatory biomarkers, and tissue-specific biomarkers in KOA patients.
…
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Journal:
Authors:
- Petersen KK,
- Siebuhr AS,
- Graven-Nielsen T,
- Simonsen O,
- Boesen MP,
- Gudbergsen H,
- Karsdal MA,
- Bay-Jensen AC,
- Arendt-Nielsen L,
Cardiovascular System
30. Oct 2015
Postoperative volume balance: does stroke volume increase in Trendelenburg's position?
In healthy humans, stroke volume (SV) and cardiac output (CO) do not increase with expansion of the central blood volume by head-down tilt or administration of fluid. Here, we exposed 85 patients to Trendelenburg's position about one hour after surgery while cardiovascular variables were determined …
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Journal:
Authors:
- Frost H,
- Mortensen CR,
- Secher NH,
- Nielsen HB,
Bone, Osteoporosis
27. Oct 2015
Role of biochemical markers in the management of osteoporosis
Estrogen and bone health form a cornerstone of osteoporosis management. Diagnosis of osteoporosis is performed using bone mineral density (BMD), despite the limitations associated with this. Within the last 25 years, numerous bone turnover markers (BTM) have been developed, and this has led to a mar…
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Authors:
Rheumatology, Osteoarthritis
20. Oct 2015
Inflammation (or synovitis)-driven osteoarthritis: an opportunity for personalizing prognosis and treatment?
The disabling and painful disease osteoarthritis (OA) is the most common form of arthritis. Strong evidence suggests that a subpopulation of OA patients has a form of OA driven by inflammation. Consequently, understanding when inflammation is the driver of disease progression and which OA patients m…
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Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Jordan JM,
- Kjelgaard-Petersen CF,
- Christiansen C,
- Abramson SB,
- Attur M,
- Berenbaum F,
- Kraus V,
- Karsdal MA,
Gastrointestinal, Inflammatory Bowel Disease
1. Oct 2015
Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis
BACKGROUND AND AIMS:
A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC] and …
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Journal:
Authors:
- Mortensen JH,
- Godskesen LE,
- Jensen MD,
- Van Haaften WT,
- Klinge LG,
- Olinga P,
- Dijkstra G,
- Kjeldsen J,
- Karsdal MA,
- Bay-Jensen AC,
- Krag A,
Rheumatology, Systemic Sclerosis
1. Oct 2015
Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis
Type I IFNs are implicated in the pathophysiology of systemic sclerosis (SSc). Recently, a Phase I open-label trial was conducted with an anti-IFNAR1 receptor antibody (anifrolumab) in adult SSc patients. In this study, we aim to assess the downstream effects of anifrolumab and elucidate the role of…
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Journal:
Authors:
- Guo X,
- Higgs BW,
- Bay-Jensen AC,
- Karsdal MA,
- Yao Y,
- Roskos LK,
- White WI,
Hepatitis B/C, Hepatic System
25. Sep 2015
Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients
BACKGROUND AND AIM:
Detection of advanced fibrosis (Metavir F≥3) is important to identify patients with a high urgency of antiviral treatments vs. those whose treatment could be deferred (F≤2). The aim was to assess the diagnostic value of novel serological extracellular matrix protein fragments as…
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Journal:
Authors:
- Nielsen MJ,
- Kazankov K,
- Leeming DJ,
- Karsdal MA,
- Krag A,
- Barrera F,
- McLeod D,
- George J,
- Grønbæk H,
Bone, Osteoporosis
8. Sep 2015
Null mutation of chloride channel 7 (Clcn7) impairs dental root formation but does not affect enamel mineralization
ClC-7, located in late endosomes and lysosomes, is critical for the function of osteoclasts. Secretion of Cl(-) by the ruffled border of osteoclasts enables H(+) secretion by v-H(+)-ATPases to dissolve bone mineral. Mice lacking ClC-7 show altered lysosomal function that leads to severe lysosomal st…
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Journal:
Authors:
- Guo J,
- Bervoets TJ,
- Henriksen K,
- Everts V,
- Bronckers AL,
Endocrinology, Type 2-Diabetes
5. Sep 2015
KBP-042 improves bodyweight and glucose homeostasis with indices of increased insulin sensitivity irrespective of route of administration
KBP-042 is a synthetic peptide dual amylin- and calcitonin-receptor agonist (DACRA) developed to treat type 2 diabetes by inducing a significant weight loss while improving glucose homeostasis. In this study the aim was to compare two different formulations: An oral formulation (1mg/kg) to subcutane…
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Journal:
Authors:
- Hjuler ST,
- Andreassen KV,
- Gydesen S,
- Karsdal MA,
- Henriksen K,
Bone
29. Aug 2015
Two Rare Mutations in the COL1A2 Gene Associate With Low Bone Mineral Density and Fractures in Iceland
We conducted a genome-wide association study of low bone mineral density (BMD) at the hip and spine utilizing sequence variants found through whole-genome sequencing of 2636 Icelanders. We found two rare missense mutations, p.Gly496Ala and p.Gly703Ser, in the COL1A2 gene that associate with measures…
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Journal:
Authors:
- Styrkarsdottir U,
- Thorleifsson G,
- Eiriksdottir B,
- Gudjonsson SA,
- Ingvarsson T,
- Center JR,
- Nguyen TV,
- Eisman JA,
- Christiansen C,
- Thorsteinsdottir U,
- Sigurdsson G,
- Stefansson K,
Extracellular Matrix Research
22. Aug 2015
Collagen and tissue turnover as function of age - implications for fibrosis
BACKGROUND:
The extracellular matrix (ECM) is the backbone of all tissues. It is a complex grid consisting of multiple structural proteins which each play a vital role for the function and maintenance of normal tissue function. In development and growth, tissue is being formed and elaborated (tissu…
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Journal:
Authors:
- Karsdal MA,
- Genovese F,
- Madsen EA,
- Manon-Jensen T,
- Schuppan D,
Oncology, Breast, Extracellular Matrix Research
3. Aug 2015
Collagen degradation products measured in serum can separate ovarian and breast cancer patients from healthy controls: A preliminary study
BACKGROUND:
During cancer the otherwise tightly controlled homeostasis of the extracellular matrix (ECM) is disturbed. The protein composition changes, the ECM stiffens and increased levels of proteases are secreted. The combination of these processes result in release of specific protein fragments…
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Journal:
Authors:
- Bager CL,
- Willumsen N,
- Leeming DJ,
- Smith V,
- Karsdal MA,
- Dornan D,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
1. Aug 2015
Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use
Osteoarthritis (OA) is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for OA that could serve as building blocks for describing OA and defining OA phenotypes, in short to provide unifying disease concepts for a heterogeneous disorder; and (2)…
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Journal:
Authors:
- Kraus VB,
- Blanco FJ,
- Englund M,
- Karsdal MA,
- Lohmander LS,
Alzheimer’s Disease, Central Nervous System
10. Jul 2015
Serum fragments of Tau for the differential diagnosis of Alzheimer's disease
Differential diagnosis of AD is still a challenge due to overlapping features with other types of dementia. Biomarkers for the differential diagnosis of AD can improve the diagnostic value of the disease and ensure an appropriate treatment of patients. The aim of this study was to evaluate the poten…
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Journal:
Authors:
- Inekci D,
- Henriksen K,
- Linemann T,
- Karsdal MA,
- Habib A,
- Bisgaard, C,
- Eriksen FB,
- Vilholm OJ,
Respiratory System, Idiopathic Pulmonary Fibrosis
9. Jul 2015
Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders
OBJECTIVES:
Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the…
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Journal:
Authors:
- Kristensen JH,
- Larsen L,
- Dasgupta B,
- Brodmerkel C,
- Curran M,
- Karsdal MA,
- Sand JM,
- Willumsen N,
- Knox AJ,
- Bolton CE,
- Johnson SR,
- Hägglund P,
- Svensson B,
- Leeming DJ,
Hepatic System, Non-Alcoholic Fatty Liver Disease
3. Jul 2015
Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS
BACKGROUND AND AIMS:
Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human…
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Journal:
Authors:
- Nielsen MJ,
- Lehmann J,
- Leeming DJ,
- Schierwagen R,
- Klein S,
- Jansen C,
- Strassburg CP,
- Bendtsen F,
- Møller S,
- Sauerbruch T,
- Karsdal MA,
- Krag A,
- Trebicka J,
Respiratory System, Chronic Obstructive Pulmonary Disease
1. Jul 2015
Clinical Drug Development Using Dynamic Biomarkers to Enable Personalized Health Care in COPD
Despite massive investments in the development of novel treatments for heterogeneous diseases such as COPD, the resources spent have only benefited a fraction of the population treated. Personalized health care to guide selection of a suitable patient population already in the clinical development o…
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Journal:
Authors:
- Bihlet A,
- Karsdal MA,
- Bay-Jensen AC,
- Read S,
- Kristensen JH,
- Sand JM,
- Leeming DJ,
- Andersen JR,
- Lange P,
- Vestbo J,
Renal System, Chronic Renal Disease
1. Jul 2015
Serum and urine markers of collagen degradation reflect renal fibrosis in experimental kidney diseases
BACKGROUND:
The extent of renal fibrosis in chronic kidney disease (CKD) is the best predictor for progression of most renal diseases. To date, no established biomarkers of renal fibrosis exist.
METHODS:
We measured circulating and urinary-specific matrix metalloproteinase (MMP)-generated colla…
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Journal:
Authors:
- Papasotiriou M,
- Genovese F,
- Klinkhammer BM,
- Kunter U,
- Nielsen SH,
- Karsdal MA,
- Floege J,
- Boor P,
Bone, Osteoporosis
1. Jul 2015
Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation
Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losin…
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Journal:
Authors:
- McGee-Lawrence M,
- Buckendahl P,
- Carpenter C,
- Henriksen K,
- Vaughan M,
- Donahue S,
Alzheimer’s Disease, Central Nervous System
11. Jun 2015
Relationship between serum levels of tau fragments and clinical progression of Alzheimer's disease
Enzyme-generated fragments of tau have been linked to neuronal death and may serve as serum biomarkers of cognitive loss. Two competitive ELISAs detecting an ADAM10-generated fragment (Tau-A) or a caspase-3-generated fragment (Tau-C) were measured in baseline serum samples from patients with mild to…
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Journal:
Authors:
Chronic Obstructive Pulmonary Disease, Respiratory System
11. Jun 2015
Accelerated extracellular matrix turnover during exacerbations of COPD
BACKGROUND:
Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease progress…
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Journal:
Authors:
- Sand JM,
- Knox AJ,
- Lange P,
- Sun S,
- Kristensen JH,
- Leeming DJ,
- Karsdal MA,
- Bolton CE,
- Johnson SR,
1. Jun 2015
Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study
BACKGROUND:
Idiopathic pulmonary fibrosis, a progressive and inevitably fatal disorder, has a highly variable clinical course. Biomarkers that reflect disease activity are urgently needed to inform patient management and for use as biomarkers of therapeutic response (theragnostic biomarkers) in cli…
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Journal:
Authors:
- Jenkins RG,
- Simpson JK,
- Saini G,
- Bentley JH,
- Russell AM,
- Braybrooke R,
- Molyneaux PL,
- McKeever TM,
- Wells AU,
- Flynn A,
- Hubbard RB,
- Leeming DJ,
- Marshall RP,
- Karsdal MA,
- Lukey PT,
- Maher TM,
Hepatic System, Non-Alcoholic Fatty Liver Disease
15. May 2015
Novel insights into the function and dynamics of extracellular matrix in liver fibrosis
Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential…
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Authors:
- Karsdal MA,
- Manon-Jensen T,
- Genovese F,
- Kristensen JH,
- Nielsen MJ,
- Sand JM,
- Hansen NU,
- Bay-Jensen AC,
- Bager CL,
- Krag A,
- Blanchard A,
- Krarup H,
- Leeming DJ,
- Schuppan D,
Central Nervous System, Alzheimer’s Disease
11. May 2015
Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research
The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebr…
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Journal:
Authors:
- O'Bryant SE,
- Gupta V,
- Henriksen K,
- Edwards M,
- Jeromin A,
- Lista S,
- Bazenet C,
- Soares H,
- Lovestone S,
- Hampel H,
- Montine T,
- Blennow K,
- Carrillo M,
- Graff-Radford N,
- Laske C,
- Breteler M,
- Shaw L,
- Trojanowski JQ,
- Schupf N,
- Rissman RA,
- Fagan AM,
- Oberoi P,
- Umek R,
- Weiner MW,
- Grammas P,
- Posner H,
- Martins R,
- STAR-B and BBBIG working groups,
Alzheimer’s Disease, Central Nervous System
11. May 2015
The potential of pathological protein fragmentation in blood-based biomarker development for dementia - with emphasis on Alzheimer's disease
The diagnosis of dementia is challenging and early stages are rarely detected limiting the possibilities for early intervention. Another challenge is the overlap in the clinical features across the different dementia types leading to difficulties in the differential diagnosis. Identifying biomarkers…
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Authors:
- Inekci D,
- Jonesco DS,
- Kennard S,
- Karsdal MA,
- Henriksen K,
Bone, Osteoporosis
10. May 2015
Novel targets for the prevention of osteoporosis - lessons learned from studies of metabolic bone disorders
Osteoporosis is a major health care problem, and whereas efficacious treatments for vertebral fracture reduction are available for osteoporosis patients, these therapies are still limited with respect to capacity for restoration of bone loss, as well as efficacy on non-vertebral fractures, such as h…
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Authors:
Respiratory System, Chronic Obstructive Pulmonary Disease
3. May 2015
Serological assessment of neutrophil elastase activity on elastin during lung ECM remodeling
BACKGROUND:
During the pathological destruction of lung tissue, neutrophil elastase (NE) degrades elastin, one of the major constituents of lung parenchyma. However there are no non-invasive methods to quantify NE degradation of elastin. We selected specific elastin fragments generated by NE for an…
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Journal:
Authors:
- Kristensen JH,
- Karsdal MA,
- Sand JM,
- Willumsen N,
- Diefenbach C,
- Svensson B,
- Hägglund P,
- Oersnes-Leeming DJ,
Hepatic System, Alcoholic Liver Disease
1. May 2015
Pro-C5, a marker of true type V collagen formation and fibrillation, correlates with portal hypertension in patients with alcoholic cirrhosis
BACKGROUND AND AIMS:
The hepatic venous pressure gradient (HVPG) is an important but invasive diagnostic and prognostic marker in cirrhotic patients. The aim of the study was to evaluate a novel biochemical plasma marker of true type V collagen formation (Pro-C5) for describing HVPG.
METHODS:
N…
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Journal:
Authors:
- Leeming DJ,
- Veidal SS,
- Karsdal MA,
- Nielsen MJ,
- Trebicka J,
- Busk T,
- Bendtsen F,
- Krag A,
- Møller S,
Endocrinology, Type 2-Diabetes
1. May 2015
Lessons learned from the clinical development of oral peptides
The oral delivery of peptides and proteins has been hampered by an array of obstacles. However, several promising novel oral delivery systems have been developed. This paper reviews the most advanced oral formulation technologies, and highlights key lessons and implications from studies undertaken t…
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Journal:
Authors:
- Karsdal MA,
- Riis BJ,
- Mehta N,
- Stern W,
- Arbit E,
- Christiansen C,
- Henriksen K,
Extracellular Matrix Research
30. Apr 2015
Matrix Metalloproteinase Mediated Type I Collagen Degradation - An Independent Risk Factor for Mortality in Women
Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major r…
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Journal:
Authors:
- Dragsbæk K,
- Neergaard JS,
- Hansen HB,
- Byrjalsen I,
- Alexandersen P,
- Kehlet SN,
- Bay-Jensen AC,
- Christiansen C,
- Karsdal MA,
Extracellular Matrix Research, Renal System, Chronic Renal Disease
26. Apr 2015
Turnover of type III collagen reflects disease severity and is associated with progression and microinflammation in patients with IgA nephropathy
BACKGROUND:
Renal fibrosis is the hallmark of progression to end-stage kidney disease. Non-invasive biomarkers of renal fibrosis could serve as specific end points in clinical trials and improve monitoring and stratification of patients with chronic kidney disease (CKD). To address this, we measure…
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Journal:
Authors:
- Genovese F,
- Boor P,
- Papasotiriou M,
- Leeming DJ,
- Karsdal MA,
- Floege J,
Rheumatology, Osteoarthritis
24. Apr 2015
The effect of protease inhibitors on the induction of osteoarthritis-related biomarkers in bovine full-depth cartilage explants
OBJECTIVE:
The specific degradation of type II collagen and aggrecan by matrix metalloproteinase (MMP)-9, -13 and ADAMTS-4 and -5 (aggrecanase-1 and -2) in the cartilage matrix is a critical step in pathology of osteoarthritis (OA). The aims of this study were: i) To investigate the relative contri…
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Journal:
Authors:
- He Y,
- Zheng Q,
- Jiang M,
- Christiansen TG,
- Kassem M,
- Karsdal MA,
- Bay-Jensen AC,
Clinical Data Quality
1. Apr 2015
Impact of source data verification on data quality in clinical trials: an empirical post hoc analysis of three phase 3 randomized clinical trials
AIM:
The aim of this project was to perform an empirical evaluation of the impact of on site source data verification (SDV) on the data quality in a clinical trial database to guide an informed decision on selection of the monitoring approach.
METHODS:
We used data from three randomized phase I…
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Journal:
Authors:
- Andersen JR,
- Byrjalsen I,
- Bihlet A,
- Kalakou F,
- Hoeck HC,
- Hansen G,
- Hansen HB,
- Karsdal MA,
- Riis BJ,
Rheumatology, Osteoarthritis
1. Apr 2015
OA phenotypes, rather than disease stage, drive structural progression--identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA
BACKGROUND/PURPOSE:
The aim of this study was to identify key characteristics of disease progression through investigation of the association of radiographic progression over two years with baseline Joint Space Width (JSW), Kellgren-Lawrence (KL) grade, Western Ontario and McMaster Universities Art…
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Journal:
Authors:
- Karsdal MA,
- Bihlet A,
- Byrjalsen I,
- Alexandersen P,
- Ladel C,
- Michaels M,
- Andersen JR,
- Riis BJ,
- Kraus V,
- Bay-Jensen AC,
- Christiansen C,
Extracellular Matrix Research
1. Apr 2015
The importance of extracellular matrix for cell function and in vivo likeness
OBJECTIVE:
Fibrotic diseases may be described as a disease of the extracellular matrix, where the balance between matrix formation and degradation has been shifted leading to an accumulation of matrix. Currently a fit for purpose model and readily available approach are adapted when doing cell cult…
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Journal:
Authors:
- Hansen NU,
- Genovese F,
- Leeming DJ,
- Karsdal MA,
Rheumatology, Osteoarthritis
1. Apr 2015
Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials
PURPOSE:
To evaluate the structure-modifying and symptom efficacy, as well as safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC carrier (a molecule based on Eligen(®) technology), in osteoarthritis (OA) patients with moderate to severe knee pain and joint structural d…
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Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Alexandersen P,
- Bihlet A,
- Andersen JR,
- Riis BJ,
- Bay-Jensen AC,
- Christiansen C,
- CSMC021C2301/1 investigators,
Rheumatology, Alkaptonuria
1. Mar 2015
Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy
Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-…
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Journal:
Authors:
- Nemethova M,
- Radvanszky J,
- Kadasi L,
- Ascher DB,
- Pires DE,
- Blundell TL,
- Porfirio B,
- Mannoni A,
- Santucci A,
- Milucci L,
- Sestini S,
- , Biolcati G,
- Sorge,
- Aurizi C,
- Aquaron R,
- Alsbou M,
- Marques Lourenço C,
- Ramadevi K,
- Ranganath LR,
- Gallagher JA,
- van Kan C,
- Hall AK,
- Olsson B,
- Ayoob H,
- Timmis OG,
- Le Quan Sang KH,
- Genovese F,
- Imrich R,
- Rovensky J,
- Srinivasaraghavan R,
- Bharadwaj SK,
- Spiegel R,
- Zatkova A,
Extracellular Matrix Research, Hepatitis B/C, Hepatic System
1. Feb 2015
Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C
BACKGROUND & AIMS:
Fibrogenesis results in release of certain extracellular matrix protein fragments into the circulation. We evaluated the diagnostic and prognostic performance of two novel serological markers, the precisely cleaved N-terminal propeptide of type III collagen (Pro-C3) and a peptide…
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Journal:
Authors:
- Nielsen MJ,
- Veidal SS,
- Karsdal MA,
- Leeming DJ,
- Vainer B,
- Gardner SD,
- Hamatake R,
- Goodman ZD,
- Schuppan D,
- Patel K,
1. Feb 2015
The collagen turnover profile is altered in patients with inguinal and incisional hernia
BACKGROUND:
Disturbed metabolism in the extracellular matrix (ECM) contributes to formation of abdominal wall hernias. The aim of this study was to gain deeper insight into the ECM turnover in hernia patients by analyzing serum biomarkers specifically reflecting collagen synthesis and breakdown in …
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Journal:
Authors:
- Henriksen NA,
- Mortensen JH,
- Sorensen LT,
- Bay-Jensen AC,
- Ågren MS,
- Jorgensen LN,
- Karsdal MA,
Rheumatology, Osteoarthritis
1. Jan 2015
Association between biochemical cartilage markers and clinical symptoms in patients with hip osteoarthritis: cohort study with 2-year follow-up
OBJECTIVES:
To assess associations between uCTX-II or uCIIM and severity of hip pain in patients with mild-moderate hip osteoarthritis (OA) over a 2-year period, and establish whether the level of these biomarkers at baseline could estimate a specific trajectory of hip pain.
DESIGN:
A cohort st…
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Journal:
Authors:
- Dorleijn DM,
- Luijsterburg PA,
- Bay-Jensen AC,
- Siebuhr AS,
- Karsdal MA,
- Rozendaal RM,
- Bos PK,
- Bierma-Zeinstra SM,
Rheumatology, Gout
1. Jan 2015
Investigating the Robustness and Diagnostic Potential of Extracellular Matrix Remodelling Biomarkers in Alkaptonuria
BACKGROUND AND AIM:
Alkaptonuria (AKU) clinical manifestations resemble severe arthritis. The Suitability of Nitisinone in Alkaptonuria 1 (SONIA 1) study is a dose-finding trial for nitisinone treatment of AKU patients. We tested a panel of serum and urinary biomarkers reflecting extracellular matr…
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Journal:
Authors:
- Genovese F,
- Siebuhr AS,
- Musa K,
- Gallagher JA,
- Milan AM,
- Karsdal MA,
- Rovensky J,
- Bay-Jensen AC,
- Ranganath LR,
Rheumatology, Osteoarthritis
1. Jan 2015
Identifying specific profiles in patients with different degrees of painful knee osteoarthritis based on serological biochemical and mechanistic pain biomarkers: a diagnostic approach based on cluster analysis
Biochemical and pain biomarkers can be applied to patients with painful osteoarthritis profiles and may provide more details compared with conventional clinical tools. The aim of this study was to identify an optimal combination of biochemical and pain biomarkers for classification of patients with …
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Journal:
Authors:
- Egsgaard LL,
- Eskehave TN,
- Bay-Jensen AC,
- Hoeck HC,
- Arendt-Nielsen L,
Rheumatology, Spondyloarthropathies
18. Dec 2014
Biological relevance of citrullinations: diagnostic, prognostic and therapeutic options
OBJECTIVE:
Citrullination has become a hot topic within recent years due to its involvement in diseases such as rheumatoid arthritis (RA), multiple sclerosis and fibrosis. Citrullinations are the conversion of arginine to citrulline by peptidylarginine deiminase (PAD) enzymes, which affect protein …
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Journal:
Authors:
- Gudmann NS,
- Hansen NU,
- Jensen AC,
- Karsdal MA,
- Siebuhr AS,
Rheumatology, Osteoarthritis
11. Dec 2014
Association between experimental pain biomarkers and serologic markers in patients with different degrees of painful knee osteoarthritis
OBJECTIVE:
To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.
METHODS:
The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using t…
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Journal:
Authors:
- Arendt-Nielsen L,
- Eskehave TN,
- Egsgaard LL,
- Petersen KK,
- Graven-Nielsen T,
- Hoeck HC,
- Simonsen O,
- Siebuhr AS,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
4. Dec 2014
Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment
BACKGROUND:
Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied.
METHOD…
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Journal:
Authors:
- Ranganath LR,
- Milan AM,
- Hughes AT,
- Dutton JJ,
- Fitzgerald R,
- Briggs MC,
- Bygott H,
- Psarelli EE,
- Cox TF,
- Gallagher JA,
- Jarvis JC,
- van Kan C,
- Hall AK,
- Laan D,
- Olsson B,
- Szamosi J,
- Rudebeck M,
- Kullenberg T,
- Cronlund A,
- Svensson L,
- Junestrand C,
- Ayoob H,
- Timmis OG,
- Sireau N,
- Le Quan Sang KH,
- Genovese F,
- Braconi D,
- Santucci A,
- Nemethova M,
- Zatkova A,
- McCaffrey J,
- Christensen P,
- Ross G,
- Imrich R,
- Rovensky J,
Renal System, Extracellular Matrix Research
29. Oct 2014
Association of versican turnover with all-cause mortality in patients on haemodialysis
OBJECTIVE:
Cardiovascular diseases are among the most common causes of mortality in renal failure patients undergoing haemodialysis. A high turnover rate of the proteoglycan versican, represented by the increased presence of its fragmentation products in plasma, has previously been associated with …
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Journal:
Authors:
- Genovese F,
- Karsdal MA,
- Leeming DJ,
- Scholze A,
- Tepel M,
Respiratory System, Extracellular Matrix Research
29. Oct 2014
The role of extracellular matrix quality in pulmonary fibrosis
This review discusses the role of extracellular matrix (ECM) quality in the pathogenesis of pulmonary fibrosis (PF). In PF, the highly ordered structure of collagens and elastin within the ECM of the lung is severely disrupted and lacks its original tissue quality. Discussions about the ECM have foc…
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Journal:
Authors:
- Kristensen JH,
- Karsdal MA,
- Genovese F,
- Johnson S,
- Svensson B,
- Jacobsen S,
- Hägglund P,
- Leeming DJ,
Clinical Data Quality
19. Oct 2014
Impact of Source Data Verification on data quality in clinical trials: An empirical post-hoc analysis of three phase 3 randomised clinical trials
AIM:
The aim of this project was to perform an empirical evaluation of the impact of on site source data verification (SDV) on the data quality in a clinical trial database to guide an informed decision on selection of the monitoring approach.
METHODS:
We used data from three randomized phase I…
Read the publication
Journal:
Authors:
- Andersen JR,
- Byrjalsen I,
- Bihlet AR,
- Kalakou F,
- Hoeck HC,
- Hansen G,
- Hansen HB,
- Karsdal MA,
- Riis BJ,
Osteoarthritis, Rheumatology
17. Oct 2014
Cartilage turnover reflected by metabolic processing of type II collagen: a novel marker of anabolic function in chondrocytes
The aim of this study was to enable measurement of cartilage formation by a novel biomarker of type II collagen formation. The competitive enzyme-linked immunosorbent assay (ELISA) Pro-C2 was developed and characterized for assessment of the beta splice variant of type II procollagen (PIIBNP). This …
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Journal:
Authors:
- Gudmann NS,
- Wang J,
- Hoielt S,
- Chen P,
- Siebuhr AS,
- He Y,
- Christiansen TG,
- Karsdal MA,
- Bay-Jensen AC,
Extracellular Matrix Research
9. Oct 2014
Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy
PURPOSE:
In this study we sought to determine whether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass.
METHODS:
Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competit…
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Journal:
Authors:
- Sun S,
- Henriksen K,
- Karsdal MA,
- Armbrecht G,
- Belavý DL,
- Felsenberg D,
- Rittweger J,
- Wang Y,
- Zheng Q,
- Nedergaard AF,
Oncology, Lung
3. Oct 2014
Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer
Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a…
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Journal:
Authors:
- Willumsen N,
- Bager CL,
- Leeming DJ,
- Smith V,
- Christiansen C,
- Karsdal MA,
- Dornan D,
- Bay-Jensen AC,
Hepatic System, Hepatitis B/C
29. Sep 2014
PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension
BACKGROUND:
Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM)…
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Journal:
Authors:
- Jansen C,
- Leeming DJ,
- Mandorfer M,
- Byrjalsen I,
- Schierwagen R,
- Schwabl P,
- Karsdal MA,
- Anadol E,
- Strassburg CP,
- Rockstroh J,
- Peck-Radosavljevic M,
- Møller S,
- Bendtsen F,
- Krag A,
- Reiberger T,
- Trebicka J,
Extracellular Matrix Research, Rheumatology
22. Sep 2014
Type X collagen levels are elevated in serum from human osteoarthritis patients and associated with biomarkers of cartilage degradation and inflammation
BACKGROUND:
Osteoarthritis (OA) is the most common degenerative joint disease, of which the pathogenesis is inadequately understood. Hypertrophy-like changes have been observed as part of the progression of OA. The aim of the study was to develop and characterize a novel biomarker of chondrocytes h…
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Journal:
Authors:
- He Y,
- Siebuhr AS,
- Brandt-Hansen NU,
- Wang J,
- Su D,
- Zheng Q,
- Simonsen O,
- Petersen KK,
- Arendt-Nielsen L,
- Eskehave T,
- Hoeck HC,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Rheumatoid Arthritis
20. Sep 2014
Serological biomarkers of joint tissue turnover predict tocilizumab response at baseline
Rheumatoid arthritis (RA) is an autoimmune disease characterized by polyarticular joint inflammation resulting in massive tissue turnover. The turnover is partly mediated by an up-regulation of proteolytic enzymes, such as matrix metalloproteinases (MMPs).1 Matrix metalloproteinase 3 is 1 of the MMP…
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Journal:
Authors:
- Bay-Jensen AC,
- Byrjalsen I,
- Siebuhr AS,
- Christiansen C,
- Platt A,
- Karsdal MA,
Osteoarthritis
1. Sep 2014
Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis
OBJECTIVE:
To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and loc…
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Journal:
Authors:
- Huebner JL,
- Bay-Jensen AC,
- Huffman K,
- He Y,
- Leeming DJ,
- McDaniel GE,
- Karsdal MA,
- Kraus VB,
1. Sep 2014
Combined antiretroviral therapy attenuates hepatic extracellular matrix remodeling in HIV patients assessed by novel protein fingerprint markers
OBJECTIVES:
Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade ex…
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Journal:
Authors:
- Leeming DJ,
- Anadol E,
- Schierwagen R,
- Karsdal MA,
- Byrjalsen I,
- Nielsen MJ,
- Schwarzer-Zander C,
- Boesecke C,
- Bendtsen F,
- Møller S,
- Strassburg CP,
- Spengler U,
- Krag A,
- Rockstroh J,
- Trebicka JK,
Rheumatology, Osteoarthritis
28. Aug 2014
Association Between Experimental Pain Biomarkers and Serological Markers in Patients With Different Degree of Painful Knee Osteoarthritis
OBJECTIVE:
To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.
METHODS:
The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using t…
Read the publication
Journal:
Authors:
- Arendt-Nielsen L,
- Eskehave TN,
- Egsgaard LL,
- Petersen KK,
- Graven-Nielsen T,
- Hoeck HC,
- Simonsen O,
- Siebuhr AS,
- Karsdal MA,
- Bay-Jensen AC,
Endocrinology, Type 2-Diabetes
14. Aug 2014
Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats
We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present st…
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Journal:
Authors:
- Feigh M,
- Hjuler ST,
- Andreassen KV,
- Gydesen S,
- Ottosen I,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Extracellular Matrix Research, Hepatic System
5. Aug 2014
Review article: the efficacy of biomarkers in chronic fibroproliferative diseases - early diagnosis and prognosis, with liver fibrosis as an exemplar
BACKGROUND:
Nearly 45% of all deaths are associated with chronic fibroproliferative diseases, of which the primary characteristic is altered remodelling of the extracellular matrix. A major difficulty in developing anti-fibrotic therapies is the lack of accurate and established techniques to estima…
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Journal:
Authors:
- Karsdal MA,
- Krarup H,,
- Sand JM,
- Christensen PB,
- Gerstoft J,
- Leeming DJ,
- Weis N,
- Schaffalitzky de Muckadell OB,
- Krag A,
Rheumatology, Osteoarthritis
1. Aug 2014
Biomarkers of cartilage and surrounding joint tissue
The identification and clinical demonstration of efficacy and safety of osteo- and chondro-protective drugs are met with certain difficulties. During the last few decades, the pharmaceutical industry has, in the field of rheumatology, experienced disappointments associated with the development of di…
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Journal:
Authors:
- Siebuhr AS,
- He Y,
- Gudmann NS,
- Gram A,
- Kjelgaard-Petersen CF,
- Qvist P,
- Karsdal MA,
- Bay-Jensen AC,
Endocrinology, Type 2-Diabetes
31. Jul 2014
A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats
The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet-induced obes…
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Journal:
Authors:
- Andreassen KV,
- Feigh M,
- Hjuler ST,
- Gydesen S,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Rheumatology, Osteoarthritis
23. Jul 2014
Meta-analysis identifies loci affecting levels of the potential osteoarthritis biomarkers sCOMP and uCTX-II with genome wide significance
BACKGROUND:
Research for the use of biomarkers in osteoarthritis (OA) is promising, however, adequate discrimination between patients and controls may be hampered due to innate differences. We set out to identify loci influencing levels of serum cartilage oligomeric protein (sCOMP) and urinary C-te…
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Journal:
Authors:
- Ramos YF,
- Metrustry S,
- Arden NK,
- Bay-Jensen AC,
- Beekman M,
- de Craen AJ,
- Cupples LA,
- Esko T,
- Evangelou E,
- Felson DT,
- Hart DJ,
- Ioannidis JP,
- Karsdal MA,
- Kloppenburg M,
- Lafeber F,
- Metspalu A,
- Panoutsopoulou K,
- Slagboom PE,
- Spector TD,
- van Spil EW,
- Uitterlinden AG,
- Zhu Y,
- Valdes AM,
- van Meurs JB,
- Meulenbelt I,
Bone
22. Jul 2014
A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation
Osteopetrosis due to lack of acid secretion by osteoclasts is characterized by abolished bone resorption, increased osteoclast numbers, but normal or even increased bone formation. In contrast, osteoclast-poor osteopetrosis appears to have less osteoblasts and reduced bone formation, indicating that…
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Journal:
Authors:
- Thudium CS,
- Moscatelli I,
- Flores C,
- Thomsen JS,
- Brüel A,
- Gudmann NS,
- Hauge EM,
- Karsdal MA,
- Richter J,
- Henriksen K,
Bone, Rheumatology, Osteoarthritis
6. Jun 2014
ALPHA-CTX is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis
OBJECTIVE:
To evaluate joint tissue remodeling, with urinary collagen biomarkers, uALPHA CTX and uCTXII, and their association with osteoarthritis (OA) severity, progression, and localized knee bone turnover.
METHODS:
Participants (N=149) with symptomatic and radiographic knee OA underwent fixe…
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Journal:
Authors:
- Huebner JL,
- Bay-Jensen AC,
- Huffman KM,
- He Y,
- Leeming DJ,
- McDaniel GE,
- Karsdal MA,
- Kraus VB,
Osteoarthritis
22. May 2014
Large scale meta-analysis of urinary C-terminal telopeptide, serum cartilage oligomeric protein and matrix metalloprotease degraded type II collagen and their role in prevalence, incidence and progression of osteoarthritis
OBJECTIVE:
To evaluate the role of three cartilage-derived biomarkers on osteoarthritis (OA): urinary C-terminal telopeptide (uCTX-II), serum cartilage oligomeric protein (sCOMP), and serum MMP degraded type II collagen (sC2M).
SUBJECTS AND METHODS:
Samples from 3582 individuals from the Rotter…
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Journal:
Authors:
- Valdes AM,
- Meulenbelt I,
- Chassaing E,
- Arden NK,
- Bierma-Zeinstra S,
- Hart D,
- Hofman A,
- Karsdal MA,
- Kloppenburg M,
- Kroon HM,
- Slagboom EP,
- Spector TD,
- Uitterlinden AG,
- van Meurs JB,
- Bay-Jensen AC,
Type 2-Diabetes, Obesity, Endocrinology
6. May 2014
A Novel Oral Dual Amylin and Calcitonin Receptor Agonist (KBP-042) Exerts Anti-Obesity and Anti-Diabetic Effects in Rats
The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet-induced obes…
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Journal:
Authors:
- Andreassen KV,
- Feigh M,
- Hjuler ST,
- Gydesen S,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Bone
22. Apr 2014
Decline in calcitonin receptor expression in osteocytes with age
We have previously shown that co-administration of the transient osteoclast inhibitor, salmon calcitonin (sCT), blunts the anabolic effect of parathyroid hormone (PTH) in young rats and increases osteocytic expression of the bone formation inhibitor sclerostin (Sost). To determine whether this also …
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Journal:
Authors:
- Gooi JH,
- Chia LY,
- Walsh NC,
- Karsdal MA,
- Quinn JM,
- Martin TJ,
- Sims NA,
Oncology, Breast
8. Apr 2014
Mammographic texture resemblance generalizes as an independent risk factor for breast cancer
Breast density has been established as a major risk factor for breast cancer. We have previously demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast density. We exami…
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Journal:
Authors:
- Nielsen M,
- Vachon CM,
- Scott CG,
- Chernoff K,
- Karemore G,
- Karssemeijer N,
- Lillholm M,
- Karsdal MA,
Renal System, Extracellular Matrix Research
28. Mar 2014
The extracellular matrix in the kidney: a source of novel non-invasive biomarkers of kidney fibrosis?
Interstitial fibrosis is the common endpoint of end-stage chronic kidney disease (CKD) leading to kidney failure. The clinical course of many renal diseases, and thereby of CKD, is highly variable. One of the major challenges in deciding which treatment approach is best suited for a patient but also…
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Journal:
Authors:
- Genovese F,
- Manresa AA,
- Leeming DJ,
- Karsdal MA,
- Boor P,
Osteoarthritis
19. Mar 2014
The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases
BACKGROUND:
Matrix metalloproteinase-3 (MMP-3) plays an important role in the pathology of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Measurement of active MMP-3 in clinical samples could provide information about progression of rheumatoid diseases, and potentially response to treat…
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Journal:
Authors:
- Sun S,
- Bay-Jensen AC,
- Karsdal MA,
- Siebuhr AS,
- Zheng Q,
- Maksymowych WP,
- Christiansen TG,
- Henriksen K,
Endocrinology, Type 2-Diabetes
18. Mar 2014
Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias
Salmon calcitonin (sCT) and human calcitonin (hCT) are pharmacologically distinct. However, the reason for the differences is unclear. Here we analyze the differences between sCT and hCT on the human calcitonin receptor (CT(a)R) with respect to activation of cAMP signaling, β-arrestin recruitment, l…
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Journal:
Authors:
- Andreassen KV,
- Hjuler ST,
- Furness SG,
- Sexton PM,
- Christopoulos A,
- Nosjean O,
- Karsdal MA,
- Henriksen K,
Rheumatology, Osteoarthritis
1. Mar 2014
Republished: Value of biomarkers in osteoarthritis: current status and perspectives
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of t…
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Journal:
Authors:
- Lotz M,
- Martel-Pelletier J,
- Christiansen C,
- Brandi ML,
- Bruyère O,
- Chapurlat R,
- Collette J,
- Cooper C,
- Giacovelli G,
- Kanis JA,
- Karsdal MA,
- Kraus V,
- Lems WF,
- Meulenbelt I,
- Pelletier JP,
- Raynauld JP,
- Reiter-Niesert S,
- Rizzoli R,
- Sandell LJ,
- Van Spil WE,
- Reginster JY,
Rheumatology, Osteoarthritis
6. Feb 2014
The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments?
Osteoarthritis (OA) is the most common form of arthritic disease, and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, affecting bone, cartilage and synovium that thereby presents multiple targets for treatment. This manuscript wil…
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Journal:
Authors:
- Karsdal MA,
- Bay-Jensen AC,
- Lories RJ,
- Abramson S,
- Spector T,
- Pastoureau P,
- Christiansen C,
- Attur M,
- Henriksen K,
- Goldring SR,
- Kraus V,
Rheumatology, Rheumatoid Arthritis
5. Feb 2014
Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium, cartilage, and bone in the LITHE study
OBJECTIVE:
We investigated the effects of tocilizumab (TCZ) on joint tissue remodeling in patients with moderate to severely active RA by measuring tissue-specific biomarker.
METHODS:
The LITHE biomarker study (n = 740) was a phase III study of 4- and 8-mg/kg TCZ in combination with MTX. Early …
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Journal:
Authors:
- Bay-Jensen AC,
- Platt A,
- Byrjalsen I,
- Vergnoud P,
- Christiansen C,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
27. Jan 2014
Rheumatoid arthritis - A case for Personalized Health Care?
Ethical, clinical, and economic considerations highlight the pressing need to advance the identification of optimal treatments for each individual patient. Personalized health care (PHC) may provide a significant benefit in the treatment of a number of clinical indications characterized by costly th…
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Journal:
Authors:
- Karsdal MA,
- Bay-Jensen AC,
- Henriksen K,
- Christiansen C,
- Genant HK,
- Chamberlain C,
- Platt A,
Rheumatology, Osteoarthritis
22. Jan 2014
Osteoarthritis--a case for personalized health care?
For both economic and ethical reasons, identification of the optimal treatment for each individual patient is a pressing concern, not only for the patients and their physician, but also health care payers and the pharmaceutical industry. In the field of osteoarthritis (OA) this is of particular rele…
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Journal:
Authors:
- Karsdal MA,
- Christiansen C,
- Ladel C,
- Henriksen K,
- Kraus VB,
- Bay-Jensen AC,
Bone
15. Jan 2014
Osteoclast-derived coupling factors in bone remodeling
In the bone remodeling process that takes place throughout the skeleton at bone multicellular units, intercellular communication processes are crucial. The osteoblast lineage has long been known to program osteoclast formation and hence resorption, but the preservation of bone mass and integrity req…
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Journal:
Authors:
- Henriksen K,
- Karsdal MA,
- Martin TJ,
10. Jan 2014
Developing novel blood-based biomarkers for Alzheimer's disease
Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue o…
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Journal:
Authors:
- Fillit HM,
- Weiner MW,
- Shineman DW,
- Bain LJ,
- West T,
- Ward M,
- Trushina E,
- Teeling J,
- Soares H,
- Sjøgren M,
- Sarasa M,
- O'Bryant SE,
- Mielke MM,
- Lovestone S,
- Jeromin A,
- Henriksen K,
- Grodstein F,
- Carrillo MC,
- Snyder HM,
Central Nervous System, Alzheimer’s Disease
8. Jan 2014
The future of blood-based biomarkers for Alzheimer's disease
Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease pr…
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Journal:
Authors:
- Henriksen K,
- O'Bryant SE,
- Hampel H,
- Trojanowski JQ,
- Montine TJ,
- Jeromin A,
- Blennow K,
- Lönneborg A,
- Wyss-Coray T,
- Soares H,
- Bazenet C,
- Sjögren M,
- Hu W,
- Lovestone S,
- Karsdal MA,
- Weiner MW,
- Blood-Based Biomarker Interest Group,
Rheumatology, Osteoarthritis
7. Jan 2014
Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover
OBJECTIVES:
Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive C…
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Journal:
Authors:
- Siebuhr AS,
- Petersen KK,
- Arendt-Nielsen L,
- Egsgaard LL,
- Eskehave T,
- Christiansen C,
- Simonsen O,
- Hoeck HC,
- Karsdal MA,
- Bay-Jensen AC,
Respiratory System, Chronic Obstructive Pulmonary Disease
13. Dec 2013
MMP mediated degradation of type IV collagen alpha 1 and alpha 3 chains reflects basement membrane remodeling in experimental and clinical fibrosis--validation of two novel biomarker assays
OBJECTIVES:
Fibrosis is characterized by excessive tissue remodeling resulting from altered expression of various growth factors, cytokines and proteases. We hypothesized that matrix metalloproteinase (MMP) mediated degradation of type IV collagen, a main component of the basement membrane, will re…
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Journal:
Authors:
- Sand JM,
- Larsen L,
- Hogaboam C,
- Martinez F,
- Han M,
- Røssel Larsen M,
- Nawrocki A,
- Zheng Q,
- Karsdal MA,
- Leeming DJ,
Rheumatology
12. Dec 2013
Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men
BACKROUND:
Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain …
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Journal:
Authors:
- Nedergaard A,
- Sun S,
- Karsdal MA,
- Henriksen K,
- Kjær M,
- Lou Y,
- He Y,
- Zheng Q,,
- Suetta C,
Bone
11. Dec 2013
Osteoclasts are not crucial for hematopoietic stem cell maintenance in adult mice
The osteoclast is vital for establishment of normal hematopoiesis in the developing animal. However, its role for maintenance of hematopoiesis in adulthood is more controversial. To shed more light on this process, we transplanted hematopoietic stem cells from two osteopetrotic mouse models, with la…
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Journal:
Authors:
- Flores C,
- Moscatelli I,
- Thudium CS,
- Gudmann NS,
- Thomsen JS,
- Brüel A,
- Karsdal MA,
- Henriksen K,
- Richter J,
Rheumatology, Osteoarthritis
12. Nov 2013
Value of biomarkers in osteoarthritis: current status and perspectives
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of t…
Read the publication
Journal:
Authors:
- Lotz M,
- Martel-Pelletier J,
- Christiansen C,
- Brandi ML,
- Bruyère O,
- Chapurlat R,
- Collette J,
- Cooper C,
- Giacovelli G,
- Kanis JA,
- Karsdal MA,
- Kraus V,
- Lems WF,
- Meulenbelt I,
- Pelletier JP,
- Raynauld JP,
- Reiter-Niesert S,
- Rizzoli R,
- Sandell LJ,
- Van Spil WE,
- Reginster JY,
Oncology, Pancreas
6. Nov 2013
Extracellular matrix specific protein fingerprints measured in serum can separate pancreatic cancer patients from healthy controls
BACKGROUND:
Pancreatic cancer (PC) is an aggressive disease with an urgent need for biomarkers. Hallmarks of PC include increased collagen deposition (desmoplasia) and increased matrix metalloproteinase (MMP) activity. The aim of this study was to investigate whether protein fingerprints of specifi…
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Journal:
Authors:
- Willumsen N,
- Bager CL,
- Leeming DJ,
- Smith V,
- Karsdal MA,
- Dornan D,
- Bay-Jensen AC,
Bone
5. Nov 2013
Lentiviral gene transfer of TCIRG1 into peripheral blood CD34(+) cells restores osteoclast function in infantile malignant osteopetrosis
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorpt…
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Journal:
Authors:
- Moscatelli I,
- Thudium CS,
- Flores C,
- Schulz A,
- Askmyr M,
- Gudmann NS,
- Andersen NM,
- Porras O,
- Karsdal MA,
- Villa A,
- Fasth A,
- Henriksen K,
- Richter J,
Hepatic System, Alcoholic Liver Disease
5. Nov 2013
Novel serological neo-epitope markers of extracellular matrix proteins for the detection of portal hypertension
BACKGROUND:
The hepatic venous pressure gradient (HVPG) is an invasive, but important diagnostic and prognostic marker in cirrhosis with portal hypertension (PHT). During cirrhosis, remodelling of fibrotic tissue by matrix metalloproteinases (MMPs) is a permanent process generating small fragments …
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Journal:
Authors:
- Leeming D,
- Karsdal MA,
- Bendtsen F,
- Trebicka J,
- Nielsen MJ,
- Christiansen C,
- Møller S,
- Krag A,
Rheumatology, Osteoarthritis
17. Oct 2013
Metabolic health in families enriched for longevity is associated with low prevalence of hand osteoarthritis and influences OA biomarker profiles
OBJECTIVES:
Individual metabolic characteristics and age-related changes may affect osteoarthritis (OA) risk as well as levels of potential OA biomarkers such as serum cartilage oligomeric protein (sCOMP) and urinary cross-linked C-telopeptide of type 2 collagen (uCTX2). We investigated hand OA and…
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Journal:
Authors:
- Bos SD,
- Beekman M,
- Maier AB,,
- Karsdal MA,
- Kwok WY,
- Bay-Jensen AC,
- Kloppenburg M,
- Slagboom PE,
- Meulenbelt I,
Rheumatology
16. Oct 2013
Musculoskeletal ageing and primary prevention
Loss of musculoskeletal mass and function is a natural ageing trait, reinforced by an unhealthy life style. Loss of bone (osteoporosis) and muscle (sarcopaenia) are conditions whose prevalence are increasing because of the change in population distribution in the western world towards an older mean …
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Journal:
Authors:
- Nedergaard A,
- Henriksen K,
- Karsdal MA,
- Christiansen C,
Rheumatology, Osteoarthritis
6. Oct 2013
The development and characterization of an ELISA specifically detecting the active form of cathepsin K
OBJECTIVE:
Cathepsin K plays essential roles in bone resorption and is intensely investigated as a therapeutic target for the treatment of osteoporosis. Hence an assessment of the active form of cathepsin K may provide important biological information in metabolic bone diseases, such as osteoporosi…
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Journal:
Authors:
- Sun S,
- Karsdal MA,
- Bay-Jensen AC,
- Sørensen MG,
- Zheng Q,
- Dziegiel MH,
- Maksymowych WP,
- Henriksen K,
Renal System, Chronic Renal Disease
22. Aug 2013
Association of systemic collagen type IV formation with survival among patients undergoing hemodialysis
OBJECTIVE:
The 7S domain of collagen type IV (P4NP_7S) assessed in plasma represents systemic collagen type IV formation. The objective of the study was to investigate the association of systemic collagen type IV formation with survival among patients undergoing hemodialysis.
METHODS:
We perfor…
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Journal:
Authors:
- Leeming DJ,
- Karsdal MA,
- Rasmussen LM,
- Scholze A,
- Tepel M,
Biomarker position
18. Aug 2013
Quantification of "end products" of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways -- implications for modern clinical chemistry
The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflam…
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Journal:
Authors:
Rheumatology, Osteoarthritis
14. Aug 2013
Serological identification of fast progressors of structural damage with rheumatoid arthritis
INTRODUCTION:
Rheumatoid arthritis (RA) patients with structural progression are in most need of immediate treatment to maintain tissue integrity. The serum protein fingerprint, type I collagen degradation mediated by matrix metalloproteinases (MMP)-cleavage (C1M), is a biomarker of tissue destruct…
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Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Leeming DJ,
- Plat A,
- Byrjalsen I,
- Christiansen C,
- van de Heijde D,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
1. Aug 2013
Circulating protein fragments of cartilage and connective tissue degradation are diagnostic and prognostic markers of rheumatoid arthritis and ankylosing spondylitis
Inflammation driven connective tissue turnover is key in rheumatic diseases, such as ankylosing spondylitis (AS). Few biomarkers are available for measuring disease prognosis or the efficacy of interventions applied in these tissue-related conditions. Type II collagen is the primary structural prote…
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Journal:
Authors:
- Bay-Jensen AC,
- Wichuk S,
- Byrjalsen I,
- Leeming DJ,
- Morency N,
- Christiansen C,
- Karsdal MA,
- Maksymowych WP,
Hepatic System, Alcoholic Liver Disease
30. Jul 2013
Serum markers of the extracellular matrix remodeling reflect antifibrotic therapy in bile-duct ligated rats
BACKGROUND:
Progression of liver fibrosis is characterized by synthesis and degradation of extracellular matrix (ECM). Matrix-metalloproteinases (MMP) cleave collagen fibers at a specific site and thereby generate soluble fragments of ECM (neo-epitopes). The levels of these neo-epitopes might refle…
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Journal:
Authors:
- Schierwagen R,
- Leeming DJ,
- Klein S,
- Granzow M,
- Nielsen MJ,
- Sauerbruch T,
- Krag A,
- Karsdal MA,
- Trebicka J,
Bone
29. Jul 2013
Lentiviral gene transfer of TCIRG1 into peripheral blood CD34+ cells restores osteoclast function in infantile malignant osteopetrosis
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorpt…
Read the publication
Journal:
Authors:
- Moscatelli I,
- Thudium CS,
- Flores C,
- Schulz A,
- Askmyr M,
- Gudmann KN,
- Andersen NM,
- Porras O,
- Karsdal MA,
- Villa A,
- Fasth A,
- Henriksen K,
- Richter J,
Bone
13. Jul 2013
Autosomal dominant osteopetrosis revisited: lessons from recent studies
Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the …
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Journal:
Authors:
- Bollerslev J,
- Henriksen K,
- Nielsen MF,
- Brixen K,
- Van Hul W,
Cardiovascular System, Atherosclerosis
21. Jun 2013
Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs
BACKGROUND:
Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated…
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Journal:
Authors:
- Skjøt-Arkil H,
- Clausen RE,
- Rasmussen LM,
- Wang W,
- Wang Y,
- Zheng Q,
- Mickley H,
- Saaby L,
- Diederichsen AC,
- Lambrechtsen J,
- Martinez FJ,
- Hogaboam CM,
- Han M,
- Larsen MR,
- Nawrocki A,
- Vainer B,
- Krustrup D,
- Bjørling-Poulsen M,
- Karsdal MA,
- Leeming DJ,
Extracellular Matrix Research, Cardiovascular System, Atherosclerosis
3. Jun 2013
A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease
Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current …
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Journal:
Authors:
- Barascuk N,
- Genovese F,
- Larsen L,
- Byrjalsen I,
- Zheng Q,
- Sun S,
- Hosbond S,
- Poulsen TS,
- Diederichsen A,
- Jensen JM,
- Mickley H,
- Register TC,
- Rasmussen LM,
- Leeming DJ,
- Christiansen C,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
31. May 2013
Quantification of "end products" of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways - implications for modern clinical chemistry
The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflam…
Read the publication
Journal:
Authors:
Endocrinology
29. May 2013
Menopause, estrogens and frailty
The controversy surrounding the results from the Women's Health Initiative (WHI) trials published a decade ago caused a significant decline in the use of menopausal hormone replacement therapy. However, these results have been vehemently contested and several lines of evidence suggest that in perime…
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Journal:
Authors:
- Nedergaard A,
- Henriksen K,
- Karsdal MA,
- Christiansen C,
Hepatic System
24. May 2013
Peptidyl arginine deiminase inhibitor effect on hepatic fibrogenesis in a CCl4 pre-clinical model o2,454f liver fibrosis
Having previously shown that levels of the citrullinated vimentin peptide VICM are raised in liver fibrosis in rats, we aimed to investigate whether inhibition of citrullination as measured by VICM levels could affect fibrogenesis. Methods: Fibrogenesis was evaluated by quantitative histology and ci…
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Journal:
Authors:
- Vassiliadis E,
- Veidal SS,
- Kristiansen MN,
- Hansen C,
- Jorgensen M,
- Leeming DJ,
- Karsdal MA,
Central Nervous System, Alzheimer’s Disease
22. May 2013
An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function
OBJECTIVE:
Alzheimer's disease (AD) is a devastating neurological disease characterized by pathological proteolytic cleavage of tau protein, which appears to initiate death of the neurons. The objective of this study was to investigate whether a proteolytic fragment of the tau protein could serve a…
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Journal:
Authors:
- Henriksen K,
- Wang Y,
- Sørensen MG,
- Barascuk N,
- Suhy J,
- Pedersen JT,
- Duffin KL,
- Dean RA,
- Pajak M,
- Christiansen C,
- Zheng Q,
- Karsdal MA,
Extracellular Matrix Research, Hepatic System
15. May 2013
Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases
BACKGROUND:
The proteoglycan biglycan (BGN) is involved in collagen fibril assembly and its fragmentation is likely to be associated with collagen turnover during the pathogenesis of diseases which involve dysregulated extracellular matrix remodeling (ECMR), such as rheumatoid arthritis (RA) and li…
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Journal:
Authors:
- Genovese F,
- Barascuk N,
- Larsen L,
- Nawrocki A,
- Li Y,
- Zheng Q,
- Wang J,
- Veidal SS,
- Leeming DJ,
- Karsdal MA,
Hepatic System, Alcoholic Liver Disease
14. May 2013
Peptidyl arginine deiminase inhibitor effect on hepatic fibrogenesis in a CCl4 pre-clinical model of liver fibrosis
Having previously shown that levels of the citrullinated vimentin peptide VICM are raised in liver fibrosis in rats, we aimed to investigate whether inhibition of citrullination as measured by VICM levels could affect fibrogenesis.
METHODS:
Fibrogenesis was evaluated by quantitative histology an…
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Journal:
Authors:
- Vassiliadis E,
- Veidal SS,
- Kristiansen MN,
- Hansen C,
- Jorgensen M,
- Leeming DJ,
- Karsdal M,
Rheumatology, Osteoarthritis
13. May 2013
Role of hormones in cartilage and joint metabolism: understanding an unhealthy metabolic phenotype in osteoarthritis
OBJECTIVE:
Joint health is affected by local and systemic hormones. It is well accepted that systemic factors regulate the metabolism of joint tissues, and that substantial cross-talk between tissues actively contributes to homeostasis. In the current review, we try to define a subtype of osteoarth…
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Journal:
Authors:
- Bay-Jensen AC,
- Slagboom E,
- Chen-An P,
- Alexandersen P,
- Qvist P,
- Christiansen C,
- Meulenbelt I,
- Karsdal MA,
Rheumatology, Osteoarthritis
24. Apr 2013
The development and characterization of a competitive ELISA for measuring active ADAMTS-4 in a bovine cartilage ex vivo model
ADAMTS-4 (aggrecanase1) is believed to play an important role in the degradation of aggrecan during the progression of joint diseases. ADAMTS-4 is synthesized as a latent pro-enzyme that requires the removal of the pro-domain, exposing the N-terminal neoepitope, to achieve activity. We developed a m…
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Journal:
Authors:
- He Y,
- Zheng Q,
- Simonsen O,
- Petersen KK,
- Christiansen TG,
- Karsdal MA,
- Bay-Jensen AC,
Hepatic System, Alcoholic Liver Disease
19. Apr 2013
The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters
AIM:
The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3).
METHODS:
The monoclonal antibody wa…
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Journal:
Authors:
- Nielsen MJ,
- Nedergaard AF,
- Sun S,
- Veidal SS,
- Larsen L,
- Zheng Q,
- Suetta C,
- Henriksen K,
- Christiansen C,
- Karsdal MA,
- Leeming DJ,
Rheumatology, Spondyloarthropathies
4. Apr 2013
Circulating citrullinated vimentin fragments reflect disease burden in ankylosing spondylitis and have prognostic capacity for radiographic progression
OBJECTIVE:
Ankylosing spondylitis (AS) has been considered a seronegative rheumatic disease based on absent or low levels of antibodies against citrullinated proteins. The present study was undertaken to evaluate whether a citrullinated and matrix metalloproteinase-degraded fragment of vimentin (VI…
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Journal:
Authors:
- Bay-Jensen AC,
- Karsdal MA,
- Vassiliadis E,
- Marcher-Mikkelsen K,
- Lories R,
- Christiansen C,
- Maksymowych WP,
Extracellular Matrix Research
11. Mar 2013
Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure
Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive ti…
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Journal:
Authors:
- Karsdal MA,
- Nielsen MJ,
- Sand JM,
- Henriksen K,
- Genovese F,
- Bay-Jensen AC,
- Adamkewicz JI,
- Christiansen C,
- Leeming DJ,
Endocrinology
4. Mar 2013
Serological muscle loss biomarkers: an overview of current concepts and future possibilities
BACKGROUND:
The skeletal muscle mass is the largest organ in the healthy body, comprising 30-40 % of the body weight of an adult man. It confers protection from trauma, locomotion, ventilation, and it represents a "sink" in glucose metabolism and a reservoir of amino acids to other tissues such as …
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Journal:
Authors:
- Nedergaard A,
- Karsdal MA,
- Sun S,
- Henriksen K,
Bone
3. Mar 2013
Evaluation of the efficacy, safety and pharmacokinetic profile of oral recombinant human parathyroid hormone [rhPTH(1-31)NH(2)] in postmenopausal women with osteoporosis
CONTEXT:
Treatment of osteoporosis with subcutaneous (SC) injections of rhPTH(1-34) or rhPTH(1-84) is associated with significant improvements in BMD and reductions in osteoporotic fractures. However, subcutaneous injections can be associated with discomfort and thus deteriorating compliance.
OB…
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Journal:
Authors:
- Henriksen K,
- Andersen JR,
- Riis BJ,
- Mehta N,
- Tavakkol R,
- Alexandersen P,
- Byrjalsen I,
- Valter I,
- Nedergaard BS,
- Teglbjaerg CS,
- Stern W,
- Sturmer A,
- Mitta S,
- Nino AJ,
- Fitzpatrick LA,
- Christiansen C,
- Karsdal MA,
Hepatic System, Alcoholic Liver Disease
3. Mar 2013
Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis--a serological evaluation
BACKGROUND/AIM:
We investigated nine novel biomarkers of extracellular matrix (ECM) remodelling in a rat model of liver fibrosis.
METHODS:
Liver fibrosis was induced in 52 male Wistar rats by inhalation of carbon tetrachloride and the level of hepatic fibrosis was assessed by Sirius red stainin…
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Journal:
Authors:
- Leeming DJ,
- Byrjalsen I,
- Jiménez W,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
14. Feb 2013
Investigation of chondrocyte hypertrophy and cartilage calcification in a full-depth articular cartilage explants model
Articular cartilage deterioration, which includes cartilage degradation and chondrocyte hypertrophy, is a hallmark of degenerative joint diseases (DJD). Chondrocyte hypertrophy is initiated in the deep layer of the cartilage; thus, a robust explants model for investigation of hypertrophy should incl…
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Journal:
Authors:
- Chen-An P,
- Andreassen KV,
- Henriksen K,
- Karsdal MA,
- Bay-Jensen AC,
Endocrinology, Type 2-Diabetes
4. Feb 2013
Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats
OBJECTIVE:
Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects …
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Journal:
Authors:
- Feigh M,
- Andreassen KV,
- Hjuler ST,
- Nielsen RH,
- Christiansen C,
- Henriksen K,
- Karsdal MA,
Cardiovascular System, Atherosclerosis
21. Jan 2013
Atherofibrosis - a unique and common process of the disease pathogenesis of atherosclerosis and fibrosis - lessons for biomarker development
The hallmark of a variety of fibrotic diseases such as liver fibrosis, lung fibrosis, skin fibrosis and atherosclerosis is extensive extracellular matrix remodeling (ECMr) of the disease affected tissue. Inflammation often leads to tissue disruption and destruction, upon which locally released batte…
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Journal:
Authors:
- Vassiliadis E,
- Barascuk N,
- Karsdal MA,
Rheumatology, Osteoarthritis
3. Jan 2013
Bringing cancer serological diagnosis to a new level: focusing on HER2, protein ectodomain shedding and neoepitope technology
Cancer is a heterogeneous disease and consequently an exact diagnosis is as important as the actual therapy. Therefore, identification of novel diagnostic biomarker targets is urgently needed. Physiological and pathological changes are reflected by post-translational modifications of proteins. Each …
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Journal:
Authors:
- Wang J,
- Willumsen N,
- Zheng Q,
- Xue Y,
- Karsdal M,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
18. Dec 2012
The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet?
The female predominance of polyarticular osteoarthritis (OA), and in particular the marked increase of OA in women after the menopause points to a likely involvement of female sex hormones in the maintenance of cartilage homeostasis. This perception has inspired many research groups to investigate t…
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Authors:
Hepatic System, Alcoholic Liver Disease
13. Dec 2012
Phosphodiesterase inhibition mediates matrix metalloproteinase activity and the level of collagen degradation fragments in a liver fibrosis ex vivo rat model
BACKGROUND:
Accumulation of extracellular matrix (ECM) and increased matrix metalloproteinase (MMP) activity are hallmarks of liver fibrosis. The aim of the present study was to develop a model of liver fibrosis combining ex vivo tissue culture of livers from CCl(4) treated animals with an ELISA de…
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Journal:
Authors:
- Veidal SS,
- Nielsen MJ,
- Leeming DJ,
- Karsdal MA,
Central Nervous System, Alzheimer’s Disease
12. Dec 2012
Will posttranslational modifications of brain proteins provide novel serological markers for dementias?
Drug development for dementias is significantly hampered by the lack of easily accessible biomarkers. Fluid biomarkers of dementias provide indications of disease stage, but have little prognostic value, cannot detect early pathological changes, and can only be measured in CSF (cerebrospinal fluid) …
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Journal:
Authors:
- Wang Y,
- Sørensen MG,
- Zheng Q,
- Zhang C,
- Karsdal MA,
- Henriksen K,
Rheumatology, Spondyloarthropathies
17. Nov 2012
Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study
Ankylosing spondylitis (AS) is characterized by gradual cementation of the vertebrae, a process that is described by excessive extracellular matrix remodeling. Specific matrix metalloproteinase (MMP)-derived collagen fragments are released to the circulation, and measurement of those might act as bi…
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Journal:
Authors:
- Bay-Jensen AC,
- Leeming DJ,
- Kleyer A,
- Veidal SS,
- Schett G,
- Karsdal MA,
Bone, Osteoporosis
28. Oct 2012
Recommendations on the management of fragility fracture risk in women younger than 70 years
The risk for fragility fracture represents a problem of enormous magnitude. It is estimated that only a small fraction of women with this risk take the benefit of preventive measures. The relationship between estrogen and bone mass is well known as they are the other factors related to the risk for …
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Journal:
Authors:
- Palacios S,
- Christiansen C,
- Sánchez Borrego R,
- Gambacciani M,
- Hadji P,
- Karsdal MA,
- Lambrinoudaki I,
- Lello S,
- O'Beirne B,
- Romao F,
- Rozenberg S,
- Stevenson JC,
- Ben-Rafael Z,
Endocrinology, Type 1-Diabetes
10. Oct 2012
Future detection and monitoring of diabetes may entail analysis of both β-cell function and volume: how markers of β-cell loss may assist
Disease heterogeneity is as major issue in Type II Diabetes Mellitus (T2DM), and this patient inter-variability might not be sufficiently reflected by measurements of glycated haemoglobin (HbA1c).Β-cell dysfunction and β-cell death are initiating factors in development of T2DM. In fact, β-cells are …
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Andreassen KV,
- Hjuler ST,
- Feigh M,
- Bay-Jensen AC,
- Zheng Q,
- Henriksen K,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
4. Oct 2012
IL-6 receptor inhibition positively modulates bone balance in rheumatoid arthritis patients with an inadequate response to anti-tumor necrosis factor therapy: biochemical marker analysis of bone metabolism in the tocilizumab RADIATE study (NCT00106522)
OBJECTIVE:
To evaluate changes in biochemical markers of bone metabolism in response to tocilizumab in patients with anti-tumor necrosis factor-refractory rheumatoid arthritis (RA).
METHODS:
RADIATE was a randomized, double-blind, placebo-controlled, parallel-group phase 3 trial. C-reactive pro…
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Journal:
Authors:
- Karsdal MA,
- Schett G,
- Emery P,
- Harari O,
- Byrjalsen I,
- Kenwright A,
- Bay-Jensen AC,
- Platt A,
Rheumatology, Rheumatoid Arthritis
20. Sep 2012
Matrix metalloproteinase-dependent turnover of cartilage, synovial membrane, and connective tissue is elevated in rats with collagen induced arthritis
BACKGROUND:
Rheumatoid arthritis is a disease affecting the extracellular matrix of especially synovial joints. The thickness of the synovial membrane increases and surrounding tissue degrades, leading to altered collagen balance in the tissues. In this study, we investigated the altered tissue bal…
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Journal:
Authors:
- Siebuhr AS,
- Wang J,
- Karsdal MA,
- Bay-Jensen AC,
- Y J,
- Q Z,
Endocrinology, Type 2-Diabetes
16. Sep 2012
Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats
BACKGROUND AND PURPOSE:
Oral salmon calcitonin (sCT), a dual-action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet-induced obese rats. Here, we have evaluated the anti-diabetic efficacy of oral sCT using parameters of glycaemic control and beta-cell morphology in male …
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Journal:
Authors:
- Feigh M,
- Andreassen KV,
- Neutzsky-Wulff AV,
- Petersen ST,
- Hansen C,
- Bay-Jensen AC,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Henriksen K,
- Karsdal MA,
Bone
16. Sep 2012
A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts
Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium was c…
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Journal:
Authors:
- Henriksen K,
- Andreassen KV,
- Thudium CS,
- Gudmann KN,
- Moscatelli I,
- Crüger-Hansen CE,
- Schulz AS,
- Dziegiel MH,
- Richter J,
- Karsdal MA,
- Neutzsky-Wulff AV,
Respiratory System, Idiopathic Pulmonary Fibrosis, Chronic Obstructive Pulmonary Disease
20. Jul 2012
Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation
BACKGROUND:
Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in …
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Journal:
Authors:
- Skjøt-Arkil H,
- Clausen RE,
- Nguyen QH,
- Wang Y,
- Zheng Q,
- Martinez FJ,
- Hogaboam CM,
- Han M,
- Klickstein LB,
- Larsen MR,
- Nawrocki A,
- Leeming DJ,
- Karsdal MA,
Respiratory System, Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis
11. Jul 2012
Serological investigation of the collagen degradation profile of patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis
In both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), abnormally high collagen remodeling occurs within the lung tissue. Matrix metalloproteinase (MMP)-degraded type I, III, IV, V and VI collagen and a disintegrin and metalloproteinase with thrombospondin moti…
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Journal:
Authors:
- Leeming DJ,
- Sand JM,
- Nielsen MJ,
- Genovese F,
- Martinez FJ,
- Hogaboam CM,
- Han MK,
- Klickstein LB,
- Karsdal MA,
Extracellular Matrix Research, Cardiovascular System, Acute Myocardial Infarct
6. Jul 2012
Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker
BACKGROUND:
Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical s…
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Journal:
Authors:
- Vassiliadis E,
- Rasmussen LM,
- Byrjalsen I,
- Larsen DV,
- Chaturvedi R,
- Hosbond S,
- Saabye L,
- Diederichsen AC,
- Genovese F,
- Duffin KL,
- Zheng Q,
- Chen X,
- Leeming DJ,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
1. Jul 2012
The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage
OBJECTIVE:
Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. W…
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Journal:
Authors:
- Chen-An P,
- Andreassen KV,
- Henriksen K,
- Karsdal MA,
- Bay-Jensen AC,
Hepatic System, Alcoholic Liver Disease
7. Jun 2012
Circulating levels of a collagen type v propeptide fragment in a carbon tetrachloride reversible model of liver fibrosis
AIM:
To measure levels of the collagen V formation marker CO5-1230 during liver fibrosis progression and regression.
METHODS:
Monoclonal antibodies were raised against the sequence TAALGDIMGH located at the start of the C-terminal propeptide between amino acid position 1230' and 1239' (CO5-1230…
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Journal:
Authors:
- Vassiliadis E,
- Veidal SS,
- Hansen C,
- Karsdal MA,
- Leeming DJ,
Rheumatology, Spondyloarthropathies
30. May 2012
Investigation of two novel biochemical markers of inflammation, matrix metalloproteinase and cathepsin generated fragments of C-reactive protein, in patients with ankylosing spondylitis
OBJECTIVES:
Ankylosing spondylitis (AS) is a chronic inflammation of the spine and the sacroiliac joints. Current markers of inflammation, such as C-reactive protein (CRP), are reflecting the production of an acute phase reactant rather than tissue specific inflammation, but the use of CRP as a dia…
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Journal:
Authors:
- Skjøt-Arkil H,
- Schett G,
- Zhang C,
- Larsen DV,
- Wang Y,
- Zheng Q,
- Larsen MR,
- Nawrocki A,
- Bay-Jensen AC,
- Henriksen K,
- Christiansen C,
- Alexandersen P,
- Leeming DJ,
- Karsdal MA,
Hepatic System, Alcoholic Liver Disease
16. May 2012
Enzyme-linked immunosorbent serum assay specific for the 7S domain of Collagen Type IV (P4NP 7S): A marker related to the extracellular matrix remodeling during liver fibrogenesis
AIM:
The present study describes the ability of a newly developed N-terminal pro-peptides of type IV collagen 7S domain (P4NP 7S) competitive enzyme-linked immunosorbent assay (ELISA) for describing liver fibrosis. The assay applies a monoclonal antibody specific for a PIVNP 7S epitope 100% homolog…
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Journal:
Authors:
- Leeming DJ,
- Nielsen MJ,
- Dai Y,
- Veidal SS,
- Vassiliadis E,
- Zhang C,
- He Y,
- Vainer B,
- Zheng Q,
- Karsdal MA,
Cardiovascular System, Atherosclerosis
10. May 2012
Novel cardiac-specific biomarkers and the cardiovascular continuum
The concept of the cardiovascular continuum, introduced during the early 1990s, created a holistic view of the chain of events connecting cardiovascular-related risk factors with the progressive development of pathological-related tissue remodelling and ultimately, heart failure and death. Understan…
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Journal:
Authors:
- Vassiliadis E,
- Barascuk N,
- Didangelos A,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
7. May 2012
MMP mediated type V collagen degradation (C5M) is elevated in ankylosing spondylitis
OBJECTIVES:
Type V collagen has been demonstrated to control fibril formation. The aim of this study was to develop an ELISA capable of detecting a fragment of type V collagen generated by MMP-2/9 and to evaluate the assay as biomarker for ankylosing spondylitis (AS).
DESIGN AND METHODS:
A frag…
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Journal:
Authors:
- Veidal SS,
- Larsen DV,
- Chen X,
- Sun S,
- Zheng Q,
- Bay-Jensen AC,
- Leeming DJ,
- Nawrocki A,
- Larsen MR,
- Schett G,
- Karsdal MA,
Bone
5. Apr 2012
Generation of human osteoclasts from peripheral blood
Osteoclasts are multi-nucleated cells that have the unique ability to resorb calcified bone matrix. They derive from haematopoietic precursor cells, and can be generated in vitro by stimulation of peripheral blood mononuclear cells with the cytokines M-CSF and RANKL. In this chapter, we describe the…
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Journal:
Authors:
- Henriksen K,
- Karsdal MA,
- Taylor A,
- Tosh D,
- Coxon FP,
Hepatic System, Alcoholic Liver Disease
5. Apr 2012
Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology
AIM:
To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes.
METHODS:
A monoclonal antibody against the sequence RLRSSVPGV-citrullin…
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Journal:
Authors:
- Vassiliadis E,
- Oliveira CP,
- Alvares-da-Silva MR,
- Zhang C,
- Carrilho FJ,
- Stefano JT,
- Rabelo F,
- Pereira L,
- Kappel CR,
- Henriksen K,
- Veidal SS,
- Vainer B,
- Duffin KL,
- Christiansen C,
- Leeming DJ,
- Karsdal MA,
Bone, Osteoporosis
13. Mar 2012
Disruption of the V-ATPase functionality as a way to uncouple bone formation and resorption - a novel target for treatment of osteoporosis
The unique ability of the osteoclasts to resorb the calcified bone matrix is dependent on secretion of hydrochloric acid. This process is mediated by a vacuolar H+ ATPase (V-ATPase) and a chloride-proton antiporter. The structural subunit of the V-ATPase, a3, is highly specific for osteoclasts, and …
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Journal:
Authors:
- Thudium CS,
- Jensen VK,
- Karsdal MA,
- Henriksen K,
Rheumatology, Osteoarthritis
15. Feb 2012
Mice over-expressing salmon calcitonin have strongly attenuated osteoarthritic histopathological changes after destabilization of the medial meniscus
OBJECTIVE:
Calcitonin is well-known for its inhibitory actions on bone-resorbing osteoclasts and recently potential beneficial effects on cartilage were shown. We investigated effects of salmon calcitonin (sCT) on the articular cartilage and bone, after destabilization of the medial meniscus (DMM) …
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Journal:
Authors:
- Sondergaard BC,
- Catala-Lehnen P,
- Huebner AK,
- Bay-Jensen AC,
- Schinke T,
- Henriksen K,
- Schilling S,
- Haberland M,
- Nielsen RH,
- Amling M,
- Karsdal MA,
Cardiovascular System, Atherosclerosis
10. Feb 2012
Tumor necrosis factor-α and receptor activator of nuclear factor-κB ligand augment human macrophage foam-cell destruction of extracellular matrix through protease-mediated processes
By secreting proteases such as cathepsins and matrix metalloproteinases (MMPs), macrophage foam cells may be a major cause of ruptured atherosclerotic plaques. The aims of the present study were to investigate in vitro role of human macrophage foam cells in degrading type I collagen, a major compone…
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Journal:
Authors:
- Skjøt-Arkil H,
- Barascuk N,
- Larsen L,
- Dziegiel M,
- Henriksen K,
- Karsdal MA,
Rheumatology, Osteoarthritis
18. Jan 2012
The distribution pattern of critically short telomeres in human osteoarthritic knees
INTRODUCTION
Telomere shortening is associated with a number of common age-related diseases. A role of telomere shortening in osteoarthritis (OA) has been suggested, mainly based on the assessment of mean telomere length in ex vivo expanded chondrocytes. We addressed this role directly in vivo by u…
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Journal:
Authors:
- Harbo M,
- Bendix L,
- Bay-Jensen AC,
- Graakjaer J,
- Søe K,
- Andersen TL,
- Kjaersgaard-Andersen P,
- Koelvraa S,
- Delaisse JM,
Hepatic System, Extracellular Matrix Research
3. Jan 2012
Molecular serum markers of liver fibrosis
Fibrosis is a hallmark histologic event of chronic liver diseases and is characterized by the excessive accumulation and reorganization of the extracellular matrix (ECM). The gold standard for assessment of fibrosis is liver biopsy. As this procedure has various limitations, including risk of patien…
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Journal:
Authors:
- Liu T,
- Wang X,
- Karsdal MA,
- Leeming DJ,
- Genovese F,
Cardiovascular System, Abdominal Aortic Aneurysm
11. Dec 2011
Abdominal aortic calcification quantified by the Morphological Atherosclerotic Calcification Distribution (MACD) index is associated with features of the metabolic syndrome
BACKGROUND:
Abdominal aortic calcifications (AAC) predict cardiovascular mortality. A new scoring model for AAC, the Morphological Atherosclerotic Calcification Distribution (MACD) index may contribute with additional information to the commonly used Aortic Calcification Severity (AC24) score, when…
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Journal:
Authors:
- Barascuk N,
- Ganz M,
- Nielsen M,
- Register TC,
- Rasmussen LM,
- Karsdal MA,
- Christiansen C,
Bone, Osteoporosis
11. Dec 2011
Glucocorticoids exert context-dependent effects on cells of the joint in vitro
INTRODUCTION:
Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthri…
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Journal:
Authors:
- Madsen SH,
- Andreassen KV,
- Christensen ST,
- Karsdal MA,
- Sverdrup FM,
- Bay-Jensen AC,
- Henriksen K,
Rheumatology, Osteoarthritis, Rheumatoid Arthritis
8. Dec 2011
Molecular serum and urine marker repertoire supporting clinical research on joint diseases
The need for improved analytical techniques in the study of slow, degenerative diseases such as rheumatoid arthritis and osteoarthritis has driven major efforts aimed at identifying biochemical markers of pathological processes in both diseases. A series of novel biochemical markers has surfaced and…
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Journal:
Authors:
- Qvist P,
- Bay-Jensen AC,
- Christiansen C,
- Sondergaard BC,
- Karsdal MA,
Extracellular Matrix Research, Biomarker position
14. Nov 2011
Protein fingerprints - relying on and understanding the information of serological protein measurements
In 2004, the FDA has articulated a Critical Path Initiative to improve the efficiency of product development industry-wide, and brought attention to the pressing needs of defining new tools to better assess safety and effectiveness of new products. A better understanding of protein subtypes, protein…
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Journal:
Authors:
- Karsdal MA,
- Delvin E,
- Christiansen C,
Bone
7. Nov 2011
Use of bone turnover markers in clinical osteoporosis assessment in women: current issues and future options
Monitoring bone turnover of the adult and aging skeleton is essential for optimal treatment of bone metabolic diseases, such as postmenopausal osteoporosis. Diagnosis of osteoporosis is based solely on dual-emission x-ray absorptiometry-based measurements of bone mineral density. However, within the…
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Journal:
Authors:
Hematology
22. Oct 2011
Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis
BACKGROUND:
Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of co…
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Journal:
Authors:
- Veidal SS,
- Karsdal MA,
- Nawrocki A,
- Larsen MR,
- Dai Y,
- Zheng Q,
- Hägglund P,
- Vainer B,
- Skjøt-Arkil H,
- Leeming DJ,
Extracellular Matrix Research
16. Oct 2011
Serological biochemical markers of surrogate efficacy and safety as a novel approach to drug repositioning
How do pharmaceutical companies find new uses for old or failed drugs? Is there a way to 'manage serendipity' at the very first stage of identifying compounds that could be developed into new drugs? Several approaches are now being pursued by various companies that are dedicated to drug repositionin…
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Journal:
Authors:
Hepatic System, Alcoholic Liver Disease
16. Oct 2011
A novel marker for assessment of liver matrix remodeling: an enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)
A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) and c…
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Journal:
Authors:
- Leeming DJ,
- He Y,
- Veidal SS,
- Nguyen Q,
- Larsen D,
- Koizumi M,
- Segovia-Silvestre T,
- Zhang C,
- Zheng Q,
- Sun S,
- Cao Y,
- Barkholt V,
- Hägglund P,
- Bay-Jensen A,
- Qvist P,
- Karsdal MA,
Rheumatology, Osteoarthritis
13. Oct 2011
Identification of the calcitonin receptor in osteoarthritic chondrocytes
BACKGROUND:
Preclinical and clinical studies have shown that salmon calcitonin has cartilage protective effects in joint degenerative diseases, such as osteoarthritis (OA). However, the presence of the calcitonin receptor (CTR) in articular cartilage chondrocytes is yet to be identified. In this st…
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Journal:
Authors:
- Segovia-Silvestre T,
- Bonnefond C,
- Sondergaard BC,
- Christensen T,
- Karsdal MA,
- Bay-Jensen AC,
Endocrinology, Type 2-Diabetes
13. Oct 2011
A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats
AIM:
To investigate the effects of acute and chronic administration of a novel oral formulation of salmon calcitonin (sCT) on glycaemic control, glucose homeostasis and body weight regulation in diet-induced obese (DIO) rats-an animal model of obesity-related insulin resistance and type 2 diabetes.…
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Journal:
Authors:
- Feigh M,
- Henriksen K,
- Andreassen KV,
- Hansen C,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
Hepatic System, Non-Alcoholic Fatty Liver Disease
16. Aug 2011
Immunological detection of the type V collagen propeptide fragment, PVCP-1230, in connective tissue remodeling associated with liver fibrosis
AIM:
Liver fibrosis involves excessive remodeling and deposition of fibrillar extracellular matrix (ECM) components, which leads to malfunction of the organ, causing significant morbidity and mortality. The aim of this study was to assess whether levels of a type V collagen fragment, the propeptide…
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Journal:
Authors:
- Vassiliadis E,
- Veidal SS,
- Simonsen H,
- Larsen DV,
- Vainer B,
- Chen X,
- Zheng Q,
- Karsdal MA,
- Leeming DJ,
Hepatic System, Non-Alcoholic Steatohepatitis
9. Aug 2011
Circulating CO3-610, a degradation product of collagen III, closely reflects liver collagen and portal pressure in rats with fibrosis
BACKGROUND:
Hepatic fibrosis is characterized by intense tissue remodeling, mainly driven by matrix metalloproteinases. We previously identified CO3-610, a type III collagen neoepitope generated by matrix metalloproteinase (MMP)-9, and tested its performance as a fibrosis marker in rats with bile-d…
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Journal:
Authors:
- Segovia-Silvestre T,
- Reichenbach V,
- Fernández-Varo G,
- Vassiliadis E,
- Barascuk N,
- Morales-Ruiz M,
- Karsdal MA,
- Jiménez W,
Oncology, Breast
3. Aug 2011
A novel and automatic mammographic texture resemblance marker is an independent risk factor for breast cancer
OBJECTIVE:
We investigated whether breast cancer is predicted by a breast cancer risk mammographic texture resemblance (MTR) marker.
METHODS:
A previously published case-control study included 495 women of which 245 were diagnosed with breast cancer. In baseline mammograms, 2-4 years prior to d…
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Journal:
Authors:
- Nielsen M,
- Karemore G,
- Loog M,
- Raundahl J,
- Karssemeijer N,
- Otten JD,
- Karsdal MA,
- Vachon CM,
- Christiansen C,
Bone
22. Jul 2011
Vertebral fracture risk (VFR) score for fracture prediction in postmenopausal women
SUMMARY:
Early prognosis of osteoporosis risk is not only important to individual patients but is also a key factor when screening for osteoporosis drug trial populations. We present an osteoporosis fracture risk score based on vertebral heights. The score separated individuals who sustained fractu…
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Journal:
Authors:
- Lillholm M,
- Ghosh A,
- Pettersen PC,
- de Bruijne M,
- Dam EB,
- Karsdal MA,
- Christiansen C,
- Genant HK,
- Nielsen M,
Rheumatology, Osteoarthritis
14. Jul 2011
Characterization of an Ex vivo Femoral Head Model Assessed by Markers of Bone and Cartilage Turnover
OBJECTIVE:
The pathophysiology of osteoarthritis involves the whole joint and is characterized by cartilage degradation and altered subchondral bone turnover. At present, there is a need for biological models that allow investigation of the interactions between the key cellular players in bone/cart…
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Journal:
Authors:
- Madsen SH,
- Goettrup AS,
- Thomsen G,
- Christensen ST,
- Schultz N,
- Henriksen K,
- Bay-Jensen AC,
- Karsdal MA,
Cardiovascular System, Atherosclerosis
11. Jul 2011
Development and validation of an enzyme-linked immunosorbent assay for the quantification of a specific MMP-9 mediated degradation fragment of type III collagen--A novel biomarker of atherosclerotic plaque remodeling
Degradation of collagen in the arterial wall by matrix metalloproteinases is the hallmark of atherosclerosis. We have developed an ELISA for the quantification of type III collagen degradation mediated by MMP-9 in urine.
DESIGN AND METHODS:
A monoclonal antibody targeting a specific MMP-9 genera…
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Journal:
Authors:
- Barascuk N,
- Vassiliadis E,
- Larsen L,
- Wang J,
- Zheng Q,
- Xing R,
- Cao Y,
- Crespo C,
- Lapret I,
- Sabatini M,
- Villeneuve N,
- Vilaine JP,
- Rasmussen LM,
- Register TC,
- Karsdal MA,
Bone
15. Jun 2011
Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidification
Osteoclasts degrade bone matrix by secretion of hydrochloric acid and proteases. We studied the processes involved in the degradation of the organic matrix of bone in detail and found that lysosomal acidification is involved in this process and that MMPs are capable of degrading the organic matrix i…
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Journal:
Authors:
- Henriksen K,
- Sørensen MG,
- Nielsen RH,
- Gram J,
- Schaller S,
- Dziegiel MH,
- Everts V,
- Bollerslev J,
- Karsdal MA,
Cardiovascular System, Atherosclerosis
11. Jun 2011
Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice
AIM:
Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELI…
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Journal:
Authors:
- Barascuk N,
- Vassiliadis E,
- Zheng Q,
- Wang Y,
- Wang W,
- Larsen L,
- Rasmussen LM,
- Karsdal MA,
Bone
11. Jun 2011
Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength
Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption.To shed light …
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Journal:
Authors:
- Henriksen K,
- Flores C,
- Thomsen JS,
- Brüel AM,
- Thudium CS,
- Neutzsky-Wulff AV,
- Langenbach GE,
- Sims N,
- Askmyr M,
- Martin TJ,
- Everts V,
- Karsdal MA,
- Richter J,
Hepatic System, Non-Alcoholic Fatty Liver Disease
9. Jun 2011
MMP mediated degradation of type VI collagen is highly associated with liver fibrosis--identification and validation of a novel biochemical marker assay
BACKGROUND AND AIMS:
During fibrogenesis, in which excessive remodeling of the extracellular matrix occurs, both the quantity of type VI collagen and levels of matrix metalloproteinases, including MMP-2 and MMP-9, increase significantly. Proteolytic degradation of type VI collagen into small fragme…
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Journal:
Authors:
- Veidal SS,
- Karsdal MA,
- Vassiliadis E,
- Nawrocki A,
- Larsen MR,
- Nguyen QH,
- Hägglund P,
- Luo Y,
- Zheng Q,
- Vainer B,
- Leeming DJ,
Endocrinology, Type 2-Diabetes
27. May 2011
Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy
BACKGROUND:
Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a cl…
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Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Qvist P,
- Beck-Nielsen H,
- Hansen G,
- Riis BJ,
- Perrild H,
- Svendsen OL,
- Gram J,
- Karsdal MA,
- Christiansen C,
- BALLET Trial Investigators,
Extracellular Matrix Research
16. May 2011
Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development
The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, designated neoepitopes. Neoepitopes are post-translational modifications (PTMs) of proteins and are derived by processes, such as protease cleavage, citrullination, nitrosylation, glycosylation and…
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Journal:
Authors:
- Leeming DJ,
- Bay-Jensen AC,
- Vassiliadis E,
- Larsen MR,
- Henriksen K,
- Karsdal MA,
Rheumatology, Osteoarthritis
19. Apr 2011
Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover
OBJECTIVES:
Traumatic osteoarthritis (OA) is possibly augmented by effects from loss of sex hormones. Salmon calcitonin is shown to reduce OA pathogenesis and bone resorption. We investigated the effects of oral salmon calcitonin treatment and ovariectomy on cartilage and bone pathology in a trauma…
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Journal:
Authors:
- Nielsen RH,
- Bay-Jensen AC,
- Byrjalsen I,
- Karsdal MA,
Bone, Osteoporosis
14. Apr 2011
Strontium ranelate effect in postmenopausal women with different clinical levels of osteoarthritis
OBJECTIVE:
The objective of this post hoc analysis was to investigate the effect of strontium ranelate on a cartilage degradation marker in postmenopausal women who participated in a randomized, placebo-controlled osteoporosis study. Women were stratified according to reported symptoms of osteoarth…
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Journal:
Authors:
- Alexandersen P,
- Karsdal MA,
- Byrjalsen I,
- Christiansen C,
Rheumatology, Osteoarthritis
13. Apr 2011
Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM--increased serum CIIM in subjects with severe radiographic osteoarthritis
OBJECTIVES:
In joint degenerative diseases, the collagens are degraded by matrix metalloproteinases and protein fragments are released to serum as potential biomarkers.
METHODS:
A collagen type II specific neoepitope, CIIM, was identified (…RDGAAG(1053)) by mass spectrometry. Two ELISAs against…
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Journal:
Authors:
- Bay-Jensen AC,
- Liu Q,
- Byrjalsen I,
- Li Y,
- Wang J,
- Pedersen C,
- Leeming DJ,
- Dam EB,
- Zheng Q,
- Qvist P,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
8. Apr 2011
Biochemical markers of ongoing joint damage in rheumatoid arthritis--current and future applications, limitations and opportunities
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with potentially debilitating joint inflammation, as well as altered skeletal bone metabolism and co-morbid conditions. Early diagnosis and aggressive treatment to control disease activity offers the highest likelihood of …
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Journal:
Authors:
- Karsdal MA,
- Woodworth T,
- Henriksen K,
- Maksymowych WP,
- Genant H,
- Vergnaud P,
- Christiansen C,
- Schubert T,
- Qvist P,
- Schett G,
- Platt A,
- Bay-Jensen AC,
Bone
5. Apr 2011
Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials
Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Bay-Jensen AC,
- Molloy B,
- Arnold M,
- John MR,
- Byrjalsen I,
- Azria M,
- Riis BJ,
- Qvist P,
- Christiansen C,
Rheumatology, Systemic Sclerosis
29. Mar 2011
Measurement of matrix metalloproteinase 9-mediated collagen type III degradation fragment as a marker of skin fibrosis
BACKGROUND:
The current study utilized a Bleomycin-induced model of skin fibrosis to investigate the neo-epitope CO3-610 (KNGETGPQGP), a fragment of collagen III released during matrix metalloproteinase-9 (MMP9) degradation of the protein, we have previously described as a novel biomarker for liver…
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Journal:
Authors:
- Vassiliadis E,
- Veidal SS,
- Barascuk N,
- Mullick JB,
- Clausen RE,
- Larsen L,
- Simonsen H,
- Larsen DV,
- bay,
- Segovia-Silvestre T,
- Leeming DJ,
- Karsdal MA,
Hepatic System, Alcoholic Liver Disease
24. Mar 2011
Measurement of CO3-610, a potential liver biomarker derived from matrix metalloproteinase-9 degradation of collagen type III, in a rat model of reversible carbon-tetrachloride-induced fibrosis
BACKGROUND AND AIM:
The current study utilized a carbon tetrachloride (CCl(4))-induced liver fibrosis model to measure levels of the MMP9-mediated collagen type III degradation fragment CO3-610 (site of cleavage: KNGETGPQGP), during disease progression and regression, and to investigate a potential…
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Journal:
Authors:
- Vassiliadis E,
- Larsen DV,
- Clausen RE,
- Veidal SS,
- Barascuk N,
- Larsen L,
- Simonsen H,
- Silvestre TS,
- Hansen C,
- Overgaard T,
- Leeming DJ,
- Karsdal MA,
Rheumatology, Osteoarthritis
15. Mar 2011
A microarray analysis of full depth knee cartilage of ovariectomized rats
BACKGROUND:
This short communication focuses the on articular cartilage and the subchondral bone, both of which play important roles in the development of osteoarthritis (OA). There are indications that estrogen-deficiency, as the post-menopausal state, accelerate the development of OA.
FINDINGS…
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Journal:
Authors:
- Bay-Jensen AC,
- Nielsen RH,
- Segovia-Silvestre T,
- Azria M,
- Staedtler F,
- Letzkus M,
- Hartmann N,
- Brachat AH,
- Karsdal MA,
Oncology, Bone
3. Mar 2011
Serum N-Terminal Propeptide of Collagen Type I is Associated with the Number of Bone Metastases in Breast and Prostate Cancer and Correlates to Other Bone Related Markers
BACKGROUND:
A number of biomarkers have been proven potentially useful for their ability to indicate bone metastases (BM) in cancer patients. The aim of this study was to investigate the relative utility of a newly developed N-terminal propeptide of collagen type I (PINP) human serum assay for the …
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Journal:
Authors:
- Leeming DJ,
- Koizumi M,
- Qvist P,
- Barkholt V,
- Zhang C,
- Henriksen K,
- Byrjalsen I,
- Karsdal MA,
Bone
15. Feb 2011
Osteoclast activity and subtypes as a function of physiology and pathology--implications for future treatments of osteoporosis
Osteoclasts have traditionally been associated exclusively with catabolic functions that are a prerequisite for bone resorption. However, emerging data suggest that osteoclasts also carry out functions that are important for optimal bone formation and bone quality. Moreover, recent findings indicate…
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Journal:
Authors:
- Henriksen K,
- Bollerslev J,
- Everts V,
- Karsdal MA,
Bone
10. Jan 2011
Imatinib mesylate does not increase bone volume in vivo
Imatinib mesylate is a tyrosine kinase inhibitor used in the management of disorders in which activation of c-Abl, PDGFR, or c-Kit signaling plays a critical role. In vitro, imatinib stimulates osteoblast differentiation, inhibits osteoblast proliferation and survival, and decreases osteoclast devel…
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Journal:
Authors:
- O'Sullivan S,
- Naot D,
- Callon KE,
- Watson M,
- Gamble GD,
- Ladefoged M,
- Karsdal MA,
- Browett P,
- Cornish J,
- Grey A,
Rheumatology, Osteoarthritis
3. Jan 2011
Tummala SDiagnosis of Osteoarthritis by Cartilage Surface Smoothness Quantified Automatically from Knee MRI
OBJECTIVE:
We investigated whether surface smoothness of articular cartilage in the medial tibiofemoral compartment quantified from magnetic resonance imaging (MRI) could be appropriate as a diagnostic marker of osteoarthritis (OA).
METHOD:
At baseline, 159 community-based subjects aged 21 to 8…
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Journal:
Authors:
- Tummala S,
- Bay-Jensen AC,
- Karsdal MA,
- Dam EB,
Cardiovascular System, Atherosclerosis
10. Nov 2010
Distribution, size, shape, growth potential and extent of abdominal aortic calcified deposits predict mortality in postmenopausal women
Aortic calcification is a major risk factor for death from cardiovascular disease. We investigated the relationship between mortality and the composite markers of number, size, morphology and distribution of calcified plaques in the lumbar aorta.
METHODS:
308 postmenopausal women aged 48-76 were…
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Journal:
Authors:
- Nielsen M,
- Ganz M,
- Lauze F,
- Pettersen PC,
- de Bruijne M,
- Clarkson TB,
- Dam EB,
- Christiansen C,
- Karsdal MA,
Bone
4. Nov 2010
A quantitative assay for lysosomal acidification rates in human osteoclasts
The osteoclast initiates resorption by creating a resorption lacuna. The ruffled border surrounding the lacunae arises from exocytosis of lysosomes. To dissolve the inorganic phase of the bone, the vacuolar adenosine triphosphatase, located in the ruffled border, pumps protons into the resorption la…
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Journal:
Authors:
- Jensen VK,
- Nosjean O,
- Dziegiel MH,
- Boutin JA,
- Sørensen MG,
- Karsdal MA,
- Henriksen K,
Hepatic System, Non-Alcoholic Fatty Liver Disease
30. Oct 2010
Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis
BACKGROUND:
During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via …
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Journal:
Authors:
- Veidal SS,
- Vassiliadis E,
- Barascuk N,
- Zhang C,
- Segovia-Silvestre T,
- Klickstein L,
- Larsen MR,
- Qvist P,
- Christiansen C,
- Vainer B,
- Karsdal MA,
Bone, Osteoporosis
26. Oct 2010
Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption
BACKGROUND:
Bone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidifi…
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Journal:
Authors:
- Sørensen MG,
- Karsdal MA,
- Dziegiel MH,
- Boutin JA,
- Nosjean O,
- Henriksen K,
Bone
10. Oct 2010
Oral salmon calcitonin--pharmacology in osteoporosis
IMPORTANCE OF THE FIELD:
Osteoporosis is a slow progressive disease with develops over decades, and where intervention is needed for an extended number of years. This highlights the need for safe intervention possibilities, which have sustained beneficial effects post-treatment.
AREAS COVERED IN…
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Journal:
Authors:
Cardiovascular System, Atherosclerosis
8. Oct 2010
Macrophage-mediated proteolytic remodeling of the extracellular matrix in atherosclerosis results in neoepitopes: a potential new class of biochemical markers
Worldwide, cardiovascular disease (CVD) is the leading cause of death. Most CVD-related deaths are caused by years of preceding atherogenesis and the extensive development of atherosclerotic plaques, some of which may rupture to cause myocardial infarction. Macrophages are known to have a role in al…
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Journal:
Authors:
- Skjøt-Arkil H,
- Barascuk N,
- Register T,
- Karsdal MA,
Bone, Osteoporosis
5. Oct 2010
Enzyme-linked immunosorbent serum assays (ELISAs) for rat and human N-terminal pro-peptide of collagen type I (PINP)--assessment of corresponding epitopes
OBJECTIVES:
The present study describes two newly developed N-terminal pro-peptides of collagen type I (PINP) competitive enzyme-linked immunosorbent assays (ELISAs) for the assessment of corresponding PINP epitopes in the rat- and human species.
METHODS:
Monoclonal antibodies were raised again…
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Journal:
Authors:
- Leeming DJ,
- Larsen DV,
- Zhang C,
- Hi Y,
- Veidal SS,
- Nielsen RH,
- Henriksen K,
- Zheng Q,
- Barkholt V,
- Riis BJ,
- Byrjalsen I,
- Qvist P,
- Karsdal MA,
Bone
15. Aug 2010
Severe developmental bone phenotype in ClC-7 deficient mice
Bone development is dependent on the functionality of three essential cell types: chondrocytes, osteoclasts and osteoblasts. If any of these cell types is dysfunctional, a developmental bone phenotype can result. The bone disease osteopetrosis is caused by osteoclast dysfunction or impaired osteocla…
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Sims NA,
- Supanchart C,
- Kornak U,
- Felsenberg D,
- Poulton IJ,
- Martin TJ,
- Karsdal MA,
- Henriksen K,
Hepatic System, Non-Alcoholic Fatty Liver Disease
10. Jul 2010
A novel assay for extracellular matrix remodeling associated with liver fibrosis: An enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen
OBJECTIVES:
Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation.
DESIGN AND METHODS:
A monoclonal antibody targeting a …
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Journal:
Authors:
- Barascuk N,
- Veidal SS,
- Larsen L,
- Larsen DV,
- Larsen MR,
- Wang J,
- Zheng Q,
- Xing R,
- Cao Y,
- Rasmussen LM,
- Karsdal MA,
Extracellular Matrix Research, Biomarker position
10. Jul 2010
Novel combinations of Post-Translational Modification (PTM) neo-epitopes provide tissue-specific biochemical markers--are they the cause or the consequence of the disease?
The aim of this review is to discuss the potential usefulness of novel advances in the class of biochemical markers, neo-epitopes. Neo-epitopes are post-translational modifications (PTMs) of proteins formed by processes such as protease cleavage, citrullination, nitrosylation, glycosylation and isom…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Leeming DJ,
- Woodworth T,
- Vassiliadis E,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
17. Jun 2010
Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis--the effect of sex, Kellgren-Lawrence (KL) score, body mass index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation
BACKGROUND:
Osteoarthritis (OA) involves changes in both bone and cartilage. These processes might be associated under some circumstances. This study investigated correlations between bone and cartilage degradation in patients with OA as a function of sex, Kellgren-Lawrence (KL) score, Body Mass In…
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Journal:
Authors:
Bone
6. Jun 2010
Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes
The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administrat…
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Journal:
Authors:
- Gooi JH,
- Pompolo S,
- Karsdal MA,
- Kulkarni NH,
- Kalajzic I,
- McAhren SH,
- Han B,
- Onyia JE,
- Ho PW,
- Walsh NC,
- Chia LY,
- Quinn JM,
- Martin TJ,
- Sims NA,
Bone, Osteoporosis
1. Jun 2010
Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption--implications for osteoclast quality
BACKGROUND:
Normal osteoclasts resorb bone by secretion of acid and proteases. Recent studies of patients with loss of function mutations affecting either of these processes have indicated a divergence in osteoclastic phenotypes. These difference in osteoclast phenotypes may directly or indirectly …
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Sørensen MG,
- Kocijancic D,
- Leeming DJ,
- Dziegiel MH,
- Karsdal MA,
- Henriksen K,
Rheumatology, Osteoarthritis
15. May 2010
Aggrecanase- and matrix metalloproteinase-mediated aggrecan degradation is associated with different molecular characteristics of aggrecan and separated in time ex vivo
Aggrecan is one of the first proteins to be depleted from articular cartilage in early osteoarthritis. We investigated the molecular differences between matrix metalloproteinase (MMP)- and aggrecanase-mediated aggrecan degradation, as a consequence of their distinct time-dependent degradation profil…
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Journal:
Authors:
- Madsen SH,
- Sumer EU,
- Bay-Jensen AC,
- Sondergaard BC,
- Qvist P,
- Karsdal MA,
Bone
15. May 2010
Should biochemical markers of bone turnover be considered standard practice for safety pharmacology
The success in biomedical sciences such as genomics and proteomics is not paralleled in the medical product development methods. The consequence of this is a lack of translation into improved drug safety and efficacy. Therefore the US Food and Drug Administration (FDA) introduced the Critical Path I…
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Journal:
Authors:
- Henriksen K,
- Bohren KM,
- Bay-Jensen AC,
- Karsdal MA,
Cardiovascular System, Atherosclerosis
21. Apr 2010
Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes
BACKGROUND:
Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular mat…
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Journal:
Authors:
- Barascuk N,
- Skjøt-Arkil H,
- Register TC,
- Larsen L,
- Byrjalsen I,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
5. Apr 2010
Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes
BACKGROUND:
Calcitonin has been demonstrated to have chondroprotective effects under pre-clinical settings. It is debated whether this effect is mediated through subchondral-bone, directly on cartilage or both in combination. We investigated possible direct effects of salmon calcitonin on proteogly…
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Journal:
Authors:
- Sondergaard BC,
- Madsen SH,
- Segovia-Silvestre T,
- Paulsen SJ,
- Christiansen T,
- Pedersen C,
- Bay-Jensen AC,
- Karsdal MA,
Hepatic System, Non-Alcoholic Fatty Liver Disease
1. Apr 2010
Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats
BACKGROUND:
Fibrosis can be described as the excess deposition of extracellular matrix (ECM) components, such as collagens and proteoglycans. Fibrosis of the liver, which eventually leads to cirrhosis, is a major global health problem. Being able to measure fibrosis progression may enable timely pr…
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Journal:
Authors:
- Veidal SS,
- Vassiliadis E,
- Bay-Jensen AC,
- Tougas G,
- Vainer B,
- Karsdal MA,
Rheumatology, Osteoarthritis
28. Feb 2010
Which elements are involved in reversible and irreversible cartilage degradation in osteoarthritis?
Osteoarthritis (OA) is a disease of the entire joint. Different treatment strategies for OA have been proposed and tested clinically without the desired efficacy. One reason for the scarcity of current chondroprotective agents may be the insufficient understanding of the patho-physiology of the join…
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Journal:
Authors:
- Bay-Jensen AC,
- Hoegh-Madsen S,
- Dam E,
- Henriksen K,
- Sondergaard BC,
- Pastoureau P,
- Qvist P,
- Karsdal MA,
Bone
18. Feb 2010
The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study
BACKGROUND:
The aim of this study was to investigate the pharmacokinetic and pharmacodynamic parameters of oral salmon calcitonin (oSCT) administered over 14 days to men and women presenting with osteoarthritis (OA).
MATERIALS AND METHODS:
The study was a phase-I, 2-week, placebo-controlled, do…
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Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Henriksen K,
- Riis BJ,
- Lau EM,
- Arnold M,
- Christiansen C,
Rheumatology, Osteoarthritis
15. Feb 2010
Application of biochemical markers in development of drugs for treatment of osteoarthritis
Osteoarthritis is a chronic disease for which no efficacious medical intervention is yet available. Recent disappointments in late-stage clinical development of disease-modifying osteoarthritic drugs (DMOADs) have precipitated efforts in biomarker discovery aimed at developing an analytical tool box…
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Journal:
Authors:
- Qvist P,
- Christiansen C,
- Karsdal MA,
- Madsen SH,
- Sondergaard BC,
- Bay-Jensen AC,
Rheumatology
8. Feb 2010
Biochemical markers of joint tissue turnover
Recent disappointments in late stage developments of anti-osteoarthritic drugs have reinforced efforts to develop better biomarkers for application in both the drug development process as well as in the routine management of these patients. Here we provide a brief review of biochemical tests availab…
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Journal:
Authors:
- Bay-Jensen AC,
- Sondergaard BC,
- Christiansen C,
- Karsdal MA,
- Madsen SH,
- Qvist P,
Rheumatology, Osteoarthritis
2. Feb 2010
Biglycan and fibromodulin have essential roles in regulating chondrogenesis and extracellular matrix turnover in temporomandibular joint osteoarthritis
The temporomandibular joint is critical for jaw movements and allows for mastication, digestion of food, and speech. Temporomandibular joint osteoarthritis is a degenerative disease that is marked by permanent cartilage destruction and loss of extracellular matrix (ECM). To understand how the ECM re…
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Journal:
Authors:
- Embree MC,
- Kilts TM,
- Ono M,
- Inkson CA,
- Syed-Picard F,
- Karsdal MA,
- Oldberg A,
- Bi Y,
- Young MF,
Extracellular Matrix Research
28. Jan 2010
Serum markers of liver fibrosis: combining the BIPED classification and the neo-epitope approach in the development of new biomarkers
BACKGROUND:
Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable eff…
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Journal:
Authors:
- Veidal SS,
- Bay-Jensen AC,
- Tougas G,
- Karsdal MA,
- Vainer B,
Bone
16. Jan 2010
Investigations of inter- and intraindividual relationships between exposure to oral salmon calcitonin and a surrogate marker of pharmacodynamic efficacy
AIMS:
The aims of the study were to investigate interindividual variations in the bioavailability of salmon calcitonin (sCT) following single oral 0.8 mg doses at three different times of the day, and intraindividual variation in sCT bioavailability at each end of a 14-day treatment period. We also…
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Journal:
Authors:
Rheumatology, Osteoarthritis
18. Dec 2009
Suppression of MMP activity in bovine cartilage explants cultures has little if any effect on the release of aggrecanase-derived aggrecan fragments
Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP- and aggrecanase-derived fr…
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Journal:
Authors:
- Wang B,
- Chen P,
- Jensen AC,
- Karsdal MA,
- Madsen SH,
- Sondergaard BC,
- Zheng Q,
- Qvist P,
Bone
10. Dec 2009
PLCL1 rs7595412 variation is not associated with hip bone size variation in postmenopausal Danish women
BACKGROUND:
Bone size (BS) variation is under strong genetic control and plays an important role in determining bone strength and fracture risk. Recently, a genome-wide association study identified polymorphisms associated with hip BS variation in the PLCL1 (phospholipase c-like 1) locus. Carriers …
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Journal:
Authors:
- Cauchi S,
- Byrjalsen I,
- Durand E,
- Karsdal MA,
- Froguel P,
Cardiovascular System, Atherosclerosis
5. Nov 2009
Long-term prevention with hormone-replacement therapy after the menopause: which women should be targeted?
For decades, hormone-replacement therapy (HRT) was considered safe and was the first choice in prevention of postmenopausal osteoporosis induced by estrogen deficiency. Numerous experimental and epidemiological studies further supported a protective effect of exogenous female sex hormones on atherog…
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Journal:
Authors:
- Alexandersen P,
- Karsdal MA,
- Christiansen C,
Bone, Osteoporosis
20. Sep 2009
Is bone quality associated with collagen age?
The World Health Organization defines osteoporosis as a systemic disease characterized by decreased bone tissue mass and microarchitectural deterioration, resulting in increased fracture risk. Since this statement, a significant amount of data has been generated showing that these two factors do not…
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Journal:
Authors:
- Leeming DJ,
- Henriksen K,
- Byrjalsen I,
- Qvist P,
- Madsen SH,
- Garnero P,
- Karsdal MA,
Endocrinology, Type 2-Diabetes
15. Aug 2009
A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats
Agonists of Perioxisome Proliferator-Activator Receptor gamma (PPARgamma), which work as insulin sensitizers, are approved for type 2 diabetes. However, adverse effects, such as oedemas, infarctions, and increased fracture rates, limit their applicability. We performed a head-to-head comparison of e…
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Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Nielsen RH,
- Madsen AN,
- Larsen LK,
- Christiansen C,
- Beck-Nielsen H,
- Karsdal MA,
Rheumatology, Osteoarthritis
24. Jul 2009
Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers
INTRODUCTION:
At present, no disease-modifying osteoarthritis drugs (DMOADS) are approved by the FDA (US Food and Drug Administration); possibly partly due to inadequate trial design since efficacy demonstration requires disease progression in the placebo group. We investigated whether combinations…
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Journal:
Authors:
- Dam EB,
- Loog M,
- Christiansen C,
- Byrjalsen I,
- Folkesson J,
- Nielsen M,
- Qazi AA,
- Pettersen PC,
- Garnero P,
- Karsdal MA,
Oncology, Breast
16. Jul 2009
Low-dose transdermal estradiol induces breast density and heterogeneity changes comparable to those of raloxifene
The aim of this study was to investigate whether transdermal low-dose estradiol treatment induces changes in mammographic density or heterogeneity compared with raloxifene, whether if these changes relate to changes in bone formation/resorption markers, and whether these findings indicate elevation …
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Journal:
Authors:
- Nielsen M,
- Raundahl J,
- Pettersen PC,
- Loog M,
- Karemore G,
- Karsdal MA,
- Christiansen C,
Rheumatology, Osteoarthritis
15. Jun 2009
Cartilage formation measured by a novel PIINP assay suggests that IGF-I does not stimulate but maintains cartilage formation ex vivo
OBJECTIVES:
The aim of this study was to investigate the time-dependent effect of insulin-like growth factor-I (IGF)-I on cartilage, evaluated by a novel procollagen type II N-terminal propeptide (PIINP) formation assay. This was performed in a cartilage model.
METHODS:
Bovine articular cartila…
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Journal:
Authors:
- Madsen SH,
- Sondergaard BC,
- Bay-Jensen AC,
- Karsdal MA,
Bone
4. Jun 2009
Local communication on and within bone controls bone remodeling
Bone remodeling is required for healthy calcium homeostasis and for repair of damage occurring with stress and age. Osteoclasts resorb bone and osteoblasts form bone. These processes normally occur in a tightly regulated sequence of events, where the amount of formed bone equals the amount of resorb…
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Journal:
Authors:
- Henriksen K,
- Neutzsky-Wulff AV,
- Bonewald LF,
- Karsdal MA,
Extracellular Matrix Research
14. May 2009
Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development
The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples of prote…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Leeming DJ,
- Mitchell P,
- Duffin K,
- Barascuk N,
- Klickstein L,
- Aggarwal P,
- Nemirovskiy O,
- Byrjalsen I,
- Qvist P,
- Bay-Jensen AC,
- Dam EB,
- Madsen SH,
- Christiansen C,
Bone
4. Apr 2009
Influence of food intake on the bioavailability and efficacy of oral calcitonin
AIMS:
To investigate the influence of food intake on the bioavailability and pharmacodynamic effects of salmon calcitonin (sCT).
METHODS:
A single-blind, randomized, partly placebo-controlled study was conducted in 36 healthy postmenopausal female volunteers aged 62-74 years. The influence of f…
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Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Azria M,
- Arnold M,
- Choi L,
- Riis BJ,
- Christiansen C,
Bone
2. Feb 2009
A pharmacokinetic and pharmacodynamic comparison of synthetic and recombinant oral salmon calcitonin
The aim of this study was to assess the bioavailability and pharmacodynamic efficacy of synthetic salmon calcitonin (ssCT) and recombinant salmon calcitonin (rsCT) in healthy postmenopausal women. The study was a single-blind, randomized study. Participants were 36 postmenopausal women 62 to 74 year…
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Journal:
Authors:
Bone
23. Jan 2009
Characterization of acid flux in osteoclasts from patients harboring a G215R mutation in ClC-7
The chloride-proton antiporter ClC-7 has been speculated to be involved in acidification of the lysosomes and the resorption lacunae in osteoclasts; however, neither direct measurements of chloride transport nor acidification have been performed. Human osteoclasts harboring a dominant negative mutat…
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Journal:
Authors:
- Henriksen K,
- Gram J,
- Neutzsky-Wulff AV,
- Jensen VK,
- Dziegiel MH,
- Bollerslev J,
- Karsdal MA,
Bone
12. Jan 2009
Advances in osteoclast biology resulting from the study of osteopetrotic mutations
Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast p…
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Journal:
Authors:
- Segovia-Silvestre T,
- Neutzsky-Wulff AV,
- Sorensen MG,
- Christiansen C,
- Bollerslev J,
- Karsdal MA,
- Henriksen K,
Bone
4. Dec 2008
Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteoporosis with oral calcitonin
BACKGROUND:
Bone resorption displays marked diurnal variation. Reversible inhibition of bone resorption may result in best possible efficacy when bone resorption peaks. The aim of the study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of 0.8 mg of oral salmon calcitonin …
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Journal:
Authors:
Bone, Osteoporosis
18. Nov 2008
Tibolone inhibits bone resorption without secondary positive effects on cartilage degradation
BACKGROUND:
Osteoarthritis is associated with increased bone resorption and increased cartilage degradation in the subchondral bone and joint. The objective of the present study was to determine whether Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties, would h…
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Journal:
Authors:
Bone
19. Sep 2008
The effects of oral calcitonin on bone collagen maturation: implications for bone turnover and quality
Anti-resorptive strategies may affect bone collagen maturation differently depending on the mode of action. Orally administrated calcitonin resulted in a dose dependent inhibition of bone resorption but did not change bone collagen maturation. This may reflect aspects of bone quality.
INTRODUCTIO…
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Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Leeming DJ,
- Delmas PD,
- Christiansen C,
Bone
8. Sep 2008
Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: the effect of water and timing of meal intake on oral delivery of Salmon Calcitonin
BACKGROUND:
To investigate the influence of water intake and dose timing on the pharmacokinetic and pharmacodynamic parameters of an oral formulation of salmon calcitonin (sCT).
METHODS:
The study was a randomized, partially-blind, placebo-controlled, single dose, exploratory crossover phase I …
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Journal:
Authors:
Bone
4. Sep 2008
Ion transporters involved in acidification of the resorption lacuna in osteoclasts
Osteoclasts possess a large amount of ion transporters, which participate in bone resorption; of these, the vacuolar-adenosine trisphosphatase (V-ATPase) and the chloride-proton antiporter ClC-7 acidify the resorption lacuna. However, whether other ion transporters participate in this process is cur…
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Journal:
Authors:
- Henriksen K,
- Sørensen MG,
- Jensen VK,
- Dziegiel MH,
- Nosjean O,
- Karsdal MA,
Rheumatology, Osteoarthritis
31. Aug 2008
Characterization of metalloprotease cleavage products of human articular cartilage
OBJECTIVE:
To identify, characterize, and compare proteolysis peptide products generated by metalloprotease digests of human articular cartilage.
METHODS:
Human articular cartilage was digested by the addition of exogenous metalloproteases, including matrix metalloproteinases 2, 3, 8, 9, 12, an…
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Journal:
Authors:
- Zhen EY,
- Brittain IJ,
- Laska DA,
- Mitchell PG,
- Sumer EU,
- Karsdal MA,
- Duffin KL,
Oncology, Bone
27. Jun 2008
Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?
BACKGROUND:
Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover in br…
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Journal:
Authors:
- Leeming DJ,
- Byrjalsen I,
- Qvist P,
- Koizumi M,
- Lynnerup N,
- Fregerslev M,
- Sørensen MG,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
16. Jun 2008
Should subchondral bone turnover be targeted when treating osteoarthritis?
OBJECTIVE:
Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, including bone and cartilage, thereby presenting alternative approaches for treatment. This re…
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Journal:
Authors:
- Karsdal MA,
- Leeming DJ,
- Dam EB,
- Henriksen K,
- Alexandersen P,
- Pastoureau P,
- Altman RD,
- Christiansen C,
Rheumatology, Osteoarthritis
6. Jun 2008
Automatic quantification of local and global articular cartilage surface curvature: biomarkers for osteoarthritis
The objective of this study was to quantitatively assess the surface curvature of the articular cartilage from low-field magnetic resonance imaging (MRI) data, and to investigate its role in populations with varying radiographic signs of osteoarthritis (OA), cross-sectionally and longitudinally. The…
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Journal:
Authors:
- Folkesson J,
- Dam EB,
- Olsen OF,
- Karsdal MA,
- Pettersen PC,
- Christiansen C,
Bone
3. Jun 2008
Characterization of the bone phenotype in ClC-7-deficient mice
Mice deficient in the chloride channel ClC-7, which is likely involved in acidification of the resorption lacuna, display severe osteopetrosis. To fully characterize the osteopetrotic phenotype, the phenotypes of osteoclasts and osteoblasts were evaluated. ClC-7(-/-) mice and their corresponding wil…
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Karsdal MA,
- Henriksen K,
Bone, Osteoporosis
17. May 2008
Biochemical markers for monitoring response to therapy: evidence for higher bone specificity by a novel marker compared with routine markers
The aim of the present study was to compare a novel marker for high bone turnover with two routine markers for screening in prostate cancer patients. The markers were evaluated in two studies: (a) a cross-sectional study of 170 prostate cancer patients with local disease stratified by +/-lymph node …
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Journal:
Authors:
- Leeming DJ,
- Hegele A,
- Byrjalsen I,
- Hofmann R,
- Qvist P,
- Karsdal MA,
- Schrader AJ,
- Wagner R,
- Olbert P,
Rheumatology, Osteoarthritis
8. May 2008
Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity
INTRODUCTION:
Physiological and pathophysiological cartilage turnover may coexist in articular cartilage. The distinct enzymatic processes leading to irreversible cartilage damage, compared with those needed for continuous self-repair and regeneration, remain to be identified. We investigated the c…
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Journal:
Authors:
- Karsdal MA,
- Madsen SH,
- Christiansen C,
- Henriksen K,
- Fosang AJ,
- Sondergaard BC,
Rheumatology, Osteoarthritis
10. Apr 2008
Oestrogen exhibits type II collagen protective effects and attenuates collagen-induced arthritis in rats
As anti-inflammatory treatments used in rheumatoid arthritis, such as glucocorticoids, often result in secondary detrimental effects on bone health, the objective of this study was to investigate the effects of oestrogen therapy (ET) on the development and activity of collagen-induced arthritis (CIA…
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Journal:
Authors:
- Nielsen RH,
- Christiansen C,
- Stolina M,
- Karsdal MA,
Bone
22. Mar 2008
Calcitonin: a drug of the past or for the future? Physiologic inhibition of bone resorption while sustaining osteoclast numbers improves bone quality
Postmenopausal osteoporosis results from a continuous imbalance between bone resorption and bone formation, favoring bone resorption. An increasing number of treatments for osteoporosis are in development and on the market. A range of differences and similarities are found between these treatment op…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Arnold M,
- Christiansen C,
Bone, Osteoporosis
19. Mar 2008
Bone turnover and bone collagen maturation in osteoporosis: effects of antiresorptive therapies
Bone collagen maturation may be important for anti-fracture efficacy as the reduction in risk is only partly explained by a concomitant increase in BMD during anti-resorptive therapy. Different treatments caused diverse profiles in bone collagen degradation products, which may have implications for …
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Journal:
Authors:
- Byrjalsen I,
- Leeming DJ,
- Qvist P,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
13. Feb 2008
Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis
The objective of this work was to investigate whether collagen degradation products in protein extract from joints could provide quantitative information on cartilage damage. Osteoarthritis (OA) was surgically induced in rat knee joints. Joints were isolated 7, 14 and 28 days after surgery for prote…
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Journal:
Authors:
- Nielsen RH,
- Stoop R,
- Leeming DJ,
- Stolina M,
- Qvist P,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
11. Feb 2008
An update review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage
OBJECTIVE:
To review cellular mechanisms that have been proposed to mediate the indirect and direct effects of estrogen on articular cartilage, and to outline the remaining clinical questions that need to be clarified before utilizing the beneficial effects of estrogen for the prevention of osteoar…
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Journal:
Authors:
- Tankó LB,
- Søndergaard BC,
- Oestergaard S,
- Karsdal MA,
- Christiansen C,
Bone
8. Feb 2008
Osteoclasts secrete non-bone derived signals that induce bone formation
Bone turnover is a highly regulated process, where bone resorption in the normal healthy individual always is followed by bone formation in a manner referred to as coupling. Patients with osteopetrosis caused by defective acidification of the resorption lacuna have severely decreased resorption, in …
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Journal:
Authors:
- Karsdal MA,
- Neutzsky-Wulff AV,
- Dziegiel MH,
- Christiansen C,
- Karsdal M,
Rheumatology, Osteoarthritis
7. Nov 2007
Calcitonin affects both bone and cartilage: a dual action treatment for osteoarthritis?
Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease involving both bone and cartilage properties, and may therefore require alternative approaches for treatment. Recent lines o…
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Journal:
Authors:
- Karsdal MA,
- Sondergaard BC,
- Arnold M,
- Christiansen C,
Bone
22. Oct 2007
Diphyllin, a novel and naturally potent V-ATPase inhibitor, abrogates acidification of the osteoclastic resorption lacunae and bone resorption
Dissolution of the inorganic phase of bone by the osteoclasts mediated by V-ATPase and ClC-7 is a prerequisite for bone resorption. Inhibitors of osteoclastic V-ATPase or ClC-7 are novel approaches for inhibition of osteoclastic bone resorption. By testing natural compounds in acidification assays, …
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Neutzsky-Wulff AV,
- Dziegiel MH,
- Karsdal MA,
Rheumatology, Osteoarthritis
14. Oct 2007
Osteoarthritic cartilage is more homogeneous than healthy cartilage: identification of a superior region of interest colocalized with a major risk factor for osteoarthritis
RATIONALE AND OBJECTIVES:
Cartilage loss as determined by magnetic resonance imaging (MRI) or joint space narrowing as determined by x-ray is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more sensitive assessment met…
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Journal:
Authors:
- Qazi AA,
- Dam EB,
- Nielsen M,
- Karsdal MA,
- Pettersen PC,
- Christiansen C,
Bone
7. Sep 2007
Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival
Osteoclasts are the sole cells possessing the ability to resorb calcified bone matrix. This occurs via secretion of hydrochloric acid mediated by the V-ATPase and the chloride channel ClC-7. Loss of acidification leads to osteopetrosis characterized by ablation of bone resorption and increased osteo…
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Journal:
Authors:
- Nielsen RH,
- Karsdal MA,
- Sørensen MG,
- Dziegiel MH,
- Henriksen K,
Rheumatology, Osteoarthritis
15. Aug 2007
The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model
OBJECTIVE:
To investigate whether oral calcitonin treatment influences the increases in type II collagen (CII) degradation and related surface erosions of articular cartilage in ovariectomized rats.
METHODS:
Fifty rats were randomly allocated into 1 of the 5 following intervention groups: sham-…
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Journal:
Authors:
- Sondergaard BC,
- Oestergaard S,
- Christiansen C,
- Tankó LB,
- Karsdal MA,
Rheumatology, Osteoarthritis
10. Aug 2007
Bone, cartilage and hormone therapy: established concepts and future scenarios
In the aftermath of the Women's Health Initiative (WHI) study, the firm ground of postmenopausal hormone therapy (HT) has been thoroughly shaken. While there was agreement that HT is indicated for the therapy of menopause-associated vasomotor symptoms and vulvovaginal atrophy, there was a general an…
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Journal:
Authors:
- Holinka CF,
- Karsdal MA,
- Christiansen C,
Bone
18. Jun 2007
Osteoclasts prefer aged bone
We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of age…
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Journal:
Authors:
- Henriksen K,
- Leeming DJ,
- Byrjalsen I,
- Nielsen RH,
- Sorensen MG,
- Dziegiel MH,
- Martin TJ,
- Christiansen C,
- Qvist P,
- Karsdal MA,
Rheumatology, Osteoarthritis
20. May 2007
Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase-mediated cartilage degradation, but not aggrecanase-mediated cartilage degradation
OBJECTIVE:
Calcitonin has been suggested to have chondroprotective effects. One signaling pathway of calcitonin is via the second messenger cAMP. We undertook this study to investigate whether increased cAMP levels in chondrocytes would be chondroprotective.
METHODS:
Cartilage degradation was i…
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Journal:
Authors:
- Karsdal MA,
- Sumer EU,
- Wulf H,
- Madsen SH,
- Christiansen C,
- Fosang AJ,
- Sondergaard BC,
Bone
18. May 2007
Assessment of osteoclast number and function: application in the development of new and improved treatment modalities for bone diseases
Numerous experimental and clinical observations suggest that overall changes in bone resorption during menopause or treatment with hormone replacement therapy (HRT) are combined effects of changes in osteoclast number and function. Moreover, due to a coupling between osteoclastic bone resorption and…
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Journal:
Authors:
- Henriksen K,
- Tankó LB,
- Qvist P,
- Delmas PD,
- Christiansen C,
- Karsdal MA,
Bone
15. May 2007
Characterization of osteoclasts derived from CD14+ monocytes isolated from peripheral blood
Bone resorption is solely mediated by osteoclasts. Therefore, a pure osteoclast population is of high interest for the investigation of biological aspects of the osteoclasts, such as the direct effect of growth factors and hormones, as well as for testing and characterizing inhibitors of bone resorp…
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Schaller S,
- Henriksen DB,
- Nielsen FC,
- Dziegiel MH,
- Karsdal MA,
Bone
12. May 2007
Biochemical markers in preclinical models of osteoporosis
Although several treatments for osteoporosis exist, further understanding of the mode of action of current treatments, as well as development of novel treatments, are of interest. Thus, preclinical models of osteoporosis are very useful, as they provide the possibility for gaining knowledge about th…
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Schaller S,
- Karsdal MA,
Rheumatology, Osteoarthritis
10. May 2007
Separation of healthy and early osteoarthritis by automatic quantification of cartilage homogeneity
OBJECTIVE:
Cartilage loss as determined either by magnetic resonance imaging (MRI) or by joint space narrowing in X-rays is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more accurate assessment method for early chang…
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Journal:
Authors:
- Qazi AA,
- Folkesson J,
- Karsdal MA,
- Christiansen C,
- Dam EB,
Bone
22. Apr 2007
Are nonresorbing osteoclasts sources of bone anabolic activity?
Some osteopetrotic mutations lead to low resorption, increased numbers of osteoclasts, and increased bone formation, whereas other osteopetrotic mutations lead to low resorption, low numbers of osteoclasts, and decreased bone formation. Elaborating on these findings, we discuss the possibility that …
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Journal:
Authors:
- Karsdal MA,
- Martin TJ,
- Bollerslev J,
- Christiansen C,
- Henriksen K,
Rheumatology, Osteoarthritis
15. Mar 2007
Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic processing of type II collagen
The aim of the present study was to investigate collagen metabolism after anabolic and catabolic stimulation of chondrocytes ex vivo.
DESIGN:
Metabolic activities in ex vivo bovine cartilage explants were stimulated with insulin-like growth factor I (IGF-I) or a combination of tumor necrosis fac…
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Journal:
Authors:
- Olsen AK,
- Sondergaard BC,
- Byrjalsen I,
- Tankó LB,
- Christiansen C,
- Müller A,
- Hein GE,
- Karsdal MA,
- Qvist P,
Rheumatology, Osteoarthritis
15. Feb 2007
MMP and non-MMP-mediated release of aggrecan and its fragments from articular cartilage: a comparative study of three different aggrecan and glycosaminoglycan assays
Aggrecan is the major proteoglycan in articular cartilage and is known to be degraded by various proteases, including matrix metalloproteinases (MMPs). The present study was undertaken to develop immunoassays detecting aggrecan and its fragments generated by MMP and non-MMP-mediated proteolysis.
…
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Journal:
Authors:
- Sumer EU,
- Sondergaard BC,
- Rousseau JC,
- Delmas PD,
- Fosang AJ,
- Karsdal MA,
- Christiansen C,
- Qvist P,
Oncology, Bone
9. Dec 2006
Biochemical approach to the detection and monitoring of metastatic bone disease: What do we know and what questions need answers?
Metastatic spread to bones frequently occurs in several types of cancer diseases, in particular breast, prostate, and lung cancer. Infiltration of bone by tumour cells is a source of several complications including severe bone pain, spinal cord compression, hypercalcemia, pathologic fractures, all r…
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Journal:
Authors:
- Tankó LB,
- Karsdal MA,
- Christiansen C,
- Leeming DJ,
Bone
25. Aug 2006
Estrogen directly attenuates human osteoclastogenesis, but has no effect on resorption by mature osteoclasts
Estrogen deficiency arising with the menopause promotes marked acceleration of bone resorption, which can be restored by hormone replacement therapy. The inhibitory effects of estrogen seem to involve indirect cytokine- mediated effects via supporting bone marrow cells, but direct estrogen-receptor …
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Dziegiel MH,
- Tankó LB,
- Karsdal MA,
Bone, Osteoporosis
16. Aug 2006
An update on biomarkers of bone turnover and their utility in biomedical research and clinical practice
BACKGROUND:
Maintenance of the structural and functional integrity of the skeleton is a critical function of a continuous remodeling driven by highly associated processes of bone resorption and synthetic activities driven by osteoclasts and osteoblasts, respectively. Acceleration of bone turnover, …
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Journal:
Authors:
- Leeming DJ,
- Alexandersen P,
- Karsdal MA,
- Qvist P,
- Schaller S,
- Tankó LB,
Rheumatology, Osteoarthritis
14. Aug 2006
Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes
OBJECTIVE:
Calcitonin was recently reported to counter progression of cartilage degradation in an experimental model of osteoarthritis, and the effects were primarily suggested to be mediated by inhibition of subchondral bone resorption. We investigated direct effects of calcitonin on chondrocytes …
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Journal:
Authors:
- Sondergaard BC,
- Wulf H,
- Henriksen K,
- Schaller S,
- Oestergaard S,
- Qvist P,
- Tankó LB,
- Bagger YZ,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
3. Aug 2006
Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: implications of the time of initiation
OBJECTIVE:
To investigate how the time of initiation influences the effects of estrogen therapy on type II collagen (CII) turnover and the structural integrity of articular cartilage in ovariectomized rats and to determine whether estrogen exerts direct effects on the catabolic function of chondroc…
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Authors:
- Oestergaard S,
- Sondergaard BC,
- Hoegh-Andersen P,
- Henriksen K,
- Qvist P,
- Christiansen C,
- Tankó LB,
- Karsdal MA,
Oncology, Bone
15. Jul 2006
Alpha CTX as a biomarker of skeletal invasion of breast cancer: immunolocalization and the load dependency of urinary excretion
We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (alphaalphaCTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localiz…
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Authors:
- Leeming DJ,
- Delling G,
- Koizumi M,
- Henriksen K,
- Karsdal MA,
- Li B,
- Qvist P,
- Tankó LB,
- Byrjalsen I,
Rheumatology, Osteoarthritis
14. Jul 2006
Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA?
OBJECTIVE:
Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. Recent observations suggest that calcitonin may act on both osteoclasts and chondrocytes. The present review was sought to summarize eme…
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Authors:
- Karsdal MA,
- Tankó LB,
- Riis BJ,
- Sondergaard BC,
- Henriksen K,
- Altman RD,
- Qvist P,
- Christiansen C,
Rheumatology, Osteoarthritis
14. Jul 2006
The utility of measuring C-terminal telopeptides of collagen type II (CTX-II) in serum and synovial fluid samples for estimation of articular cartilage status in experimental models of destructive joint diseases
OBJECTIVE:
To characterize and validate a novel, enzyme-linked immunoassay for measuring cross-linked dimer forms of C-terminal telopeptides of type II collagen (CTX-II) in serum and synovial fluid of rodents, and investigate whether CTX-II measurements can reflect joint status in two established a…
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Authors:
- Oestergaard S,
- Chouinard L,
- Doyle N,
- Karsdal MA,
- Smith SY,
- Qvist P,
- Tankó LB,
Bone
15. Jun 2006
Optimising antiresorptive therapies in postmenopausal women: why do we need to give due consideration to the degree of suppression?
Accelerated bone turnover with bone resorption exceeding bone formation is a major mechanism underlying postmenopausal bone loss and hence the development of osteoporosis. Accordingly, inhibition of bone resorption is a rational approach for the prevention of osteoporosis. In this context, the most …
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Authors:
- Karsdal MA,
- Qvist P,
- Christiansen C,
- Tankó LB,
Bone
10. Apr 2006
Mechanisms involved in skeletal anabolic therapies
Since parathyroid hormone (PTH) is the only proven anabolic therapy for bone, it becomes the benchmark by which new treatments will be evaluated. The anabolic effect of PTH is dependent upon intermittent administration, but when an elevated PTH level is maintained even for a few hours it initiates p…
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Authors:
- Martin TJ,
- Quinn JM,
- Gillespie MT,
- Ng KW,
- Karsdal M,
- Sims NA,
Rheumatology, Osteoarthritis
23. Mar 2006
Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation
OBJECTIVE:
Both matrix metalloprotease (MMP) activity and cathepsin K (CK) activity have been implicated in cartilage turnover. We investigated the relative contribution of MMP activity and CK activity in cartilage degradation using ex vivo and in vivo models.
METHODS:
Bovine articular cartilag…
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Authors:
- Søndergaard BC,
- Henriksen K,
- Wulf H,
- Oestergaard S,
- Schurigt U,
- Bräuer R,
- Danielsen I,
- Christiansen C,
- Qvist P,
- Karsdal MA,
Bone
5. Nov 2005
Osteoclasts from patients with autosomal dominant osteopetrosis type I caused by a T253I mutation in low-density lipoprotein receptor-related protein 5 are normal in vitro, but have decreased resorption capacity in vivo
Autosomal dominant osteopetrosis type I (ADOI) is presumably caused by gain-of-function mutations in the LRP5 gene. Patients with a T253I mutation in LRP5 have a high bone mass phenotype, characterized by increased mineralizing surface index but abnormally low numbers of small osteoclasts. To invest…
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Authors:
- Henriksen K,
- Gram J,
- Høegh-Andersen P,
- Jemtland R,
- Ueland T,
- Dziegiel MH,
- Schaller S,
- Bollerslev J,
- Karsdal MA,
Bone
18. Oct 2005
The role of chloride channels in osteoclasts: ClC-7 as a target for osteoporosis treatment
Chloride ions play a major role in osteoclast biology and bone homeostasis. In addition to its general cellular roles, chloride is involved in the specific bone resorption activity of osteoclasts. The chloride channel ClC-7 has been shown to be mandatory for bone resorption. It is necessary for the …
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Journal:
Authors:
- Schaller S,
- Henriksen K,
- Sørensen MG,
- Karsdal MA,
Rheumatology, Osteoarthritis
7. Jul 2005
Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis
OBJECTIVE:
To assess the efficacy of 3 months of oral salmon calcitonin (sCT) on cartilage degradation as estimated by the changes in the urinary excretion of C-terminal telopeptide of collagen type II (CTX-II), and to investigate whether the response of oral sCT to urinary CTX-II depends on the ba…
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Journal:
Authors:
- Bagger YZ,
- Tankó LB,
- Alexandersen P,
- Karsdal MA,
- Olson M,
- Mindeholm L,
- Azria M,
- Christiansen C,
Rheumatology, Osteoarthritis
1. Jul 2005
The clinical potential of estrogen for the prevention of osteoarthritis: what is known and what needs to be done?
Osteoarthritis (OA) remains a major epidemiological problem worldwide. The lack of established chondroprotective agents limits the clinical management of this disease to relief of symptoms, such as pain and joint stiffness. The marked increase in the prevalence and incidence of OA among women after …
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Journal:
Authors:
- Tankó LB,
- Karsdal MA,
- Christiansen C,
Bone
2. Jun 2005
In vitro, ex vivo, and in vivo methodological approaches for studying therapeutic targets of osteoporosis and degenerative joint diseases: how biomarkers can assist
Although our approach to the clinical management of osteoporosis (OP) and degenerative joint diseases (DJD)-major causes of disability and morbidity in the elderly-has greatly advanced in the past decades, curative treatments that could bring ultimate solutions have yet to be found or developed. Eff…
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Journal:
Authors:
- Schaller S,
- Henriksen K,
- Hoegh-Andersen P,
- Søndergaard BC,
- Sumer EU,
- Tankó LB,
- Qvist P,
- Karsdal MA,
Bone
5. Feb 2005
Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption
Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteocla