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…
Journal:
Authors:
- Nielsen PM,
- Mariager CØ,
- Mølmer M,
- Sparding N,
- Genovese F,
- Karsdal MA,
- Nørregaard R,
- Bertelsen LB,
- Laustsen C,
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…
Journal:
Authors:
- Xian X,
- Moraghebi R,
- Löfvall H,
- Fasth A,
- Henriksen K,
- Richter J,
- Woods NB,
- Moscatelli I,
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…
Journal:
Authors:
- Sinkeviciute D,
- Aspberg A,
- He Y,
- Bay-Jensen AC,
- Önnerfjord P,
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…
Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
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…
Journal:
Authors:
- Kraus VB,
- Karsdal MA,
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…
Journal:
Authors:
- Nielsen SH,
- Jonasson L,
- Kalogeropoulos K,
- Karsdal MA,
- Reese-Petersen AL,
- Auf dem Keller U,
- Genovese F,
- Nilsson J,
- Goncalves I,
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…
Journal:
Authors:
- Juhl P,
- Bay-Jensen AC,
- Hesselstrand R,
- Siebuhr AS,
- Wuttge DM,
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,…
Journal:
Authors:
- Kubo S,
- Siebuhr AS,
- Bay-Jensen AC,
- Juhl P,
- Karsdal MA,
- Satoh Y,
- Todoroki Y,
- Nakano K,
- Nakayamada S,
- Tanaka Y,
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 …
Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
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…
Journal:
Authors:
- Sonne N,
- Larsen AT,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
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…
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,
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…
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,
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…
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,
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…
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,
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 …
Journal:
Authors:
- Hodrea J,
- Balogh DB,
- Hosszu A,
- Lenart L,
- Besztercei B,
- koszegi S,
- Sparding N,
- Genovese F,
- Wagner LJ,
- Szabo AJ,
- Fekete A,
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…
Journal:
Authors:
- Reese-Petersen AL,
- Olesen MS,
- Karsdal MA,
- Svendsen J,
- Genovese F,
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…
Journal:
Authors:
- Bihlet A,
- Bjerre-Bastos JJ,
- Andersen JR,
- Byrjalsen I,
- Karsdal MA,
- Bay-Jensen AC,
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,…
Journal:
Authors:
- Langholm LL,
- Rønnow S,
- bülow Sand JM,
- Leeming DJ,
- Talsinger R,
- Miller BE,
- Vestbo J,
- Karsdal MA,
- Manon-Jensen T,
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…
Journal:
Authors:
- Bahmer T,
- Sand JMB,
- Weckmann M,
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…
Journal:
Authors:
- Worm MS,
- Bager CL,
- Blair JPM,
- Secher NH,
- Riis BJ,
- Christiansen C,
- Nielsen HB,
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…
Journal:
Authors:
- Genovese F,
- Rasmussen DGK,
- Karsdal M,
- Jesky M,
- Ferro C,
- Fenton A,
- Cockwell P,
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…
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,
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…
Journal:
Authors:
- Kjaer M,
- Frederiksen AKS,
- Nissen NI,
- Willumsen N,
- Van Hall G,
- Jorgensen LN,
- Andersen JR,
- Årgen MS,