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…
Journal:
Authors:
- Nielsen SH,
- Mouton AJ,
- DeLeon-Pennell KY,
- Genovese F,
- Karsdal MA,
- Lindsey ML,
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…
Journal:
Authors:
- Reker D,
- Kjelgaard-Petersen CF,
- Siebuhr AS,
- Michaelis M,
- Gigout A,
- Karsdal MA,
- Ladel C,
- Bay-Jensen AC,
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…
Journal:
Authors:
- Rasmussen DG,
- Fenton A,
- Jesky M,
- Ferro C,
- Boor P,
- Tepel M,
- Karsdal MA,
- Genovese F,
- Cockwell P,
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…
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,
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…
Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Karsdal MA,
- Brix S,
- Henriksen K,
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…
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,
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 …
Journal:
Authors:
- Hansen JF,
- Juul Nielsen M,
- Nyström K,
- Leeming DJ,
- Lagging M,
- Norkrans G,
- Brehm Christensen P,
- Karsdal MA,
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…
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,
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…
Journal:
Authors:
- Bay-Jensen AC,
- Thudium CS,
- Mobasheri A,
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…
Journal:
Authors:
- Bay-Jensen AC,
- Thudium CS,
- Mobasheri A,
- Gualillo O,
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…
Journal:
Authors:
- Bay-Jensen AC,
- Karsdal MA,
- Krag A,
- Kjeldsen J,
- Klinge LG,
- Hägglund P,
- Jensen MD,
- Manon-Jensen T,
- Mortensen JH,
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…
Journal:
Authors:
- Willumsen N,
- Thomsen LB,
- Bager CL,
- Jensen C,
- Karsdal MA,
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…
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,
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…
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,
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 …
Journal:
Authors:
- Bacardit J,
- Henrotin Y,
- Bierma-Zeinstra SMA,
- Thudium CS,
- Bay-Jensen AC,
- Runhaar J,
- Lazzarini N,
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…
Journal:
Authors:
- Rokamp KZ,
- Staalsø JM,
- Zaar M,
- Rasmussen P,
- Petersen LG,
- Nielsen RV,
- Secher NH,
- Olsen NV,
- Nielsen HB,
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…
Journal:
Authors:
- Husakova M,
- Siebuhr AS,
- Pavelka K,
- Spiritovic M,
- Bay-Jensen AC,
- Levitova A,
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…
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,
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…
Journal:
Authors:
- Siebuhr AS,
- Kjelgaard-Petersen CF,
- Sun S,
- Byrjalsen I,
- Christiansen C,
- Karsdal MA,
- Bay-Jensen AC,
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…
Journal:
Authors:
- Gigout A,
- Guehring H,
- Froemel D,
- Meurer A,
- Ladel C,
- Reker D,
- Bay-Jensen AC,
- Karsdal MA,
- Lindemann S,
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…
Journal:
Authors:
- Aguilera AH,
- Nielsen SH,
- Fernández-Arroyo S,
- Martín-Paredero V,
- Karsdal MA,
- Genovese F,
- Camps J,
- Joven J,
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…
Journal:
Authors:
- Karsdal MA,
- Leeming DJ,
- Brix S,
- Curran M,
- Brodmerkel C,
- Dasgupta B,
- Willumsen N,
- Bager CL,
- Kehlet SN,
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…
Journal:
Authors:
- Shahidi S,
- Hellemann D,
- Pedersen OB,
- Wetterslev J,
- Nielsen HB,
- Møller A,
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…
Journal:
Authors:
- Loeser RF,
- Beavers DP,
- Bay-Jensen AC,
- Karsdal MA,
- Nicklas BJ,
- Guermazi A,
- Hunter DJ,
- Messier SP,
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 …
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,
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…
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,
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…
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,
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 …
Journal:
Authors:
- Rasmussen LM,
- Leeming DJ,
- Karsdal MA,
- Poulsen MK,
- Christiansen AL,
- Thorsen AF,
- Preil SAR,
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-…
Authors:
- Luo Y,
- Zheng S,
- Ding Y,
- Dai Y,
- Zhou Y,
- Xiang R,
- Qvist P,
- Zheng Q,
- Bay-Jensen AC,
- Karsdal MA,
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 …
Journal:
Authors:
- Willumsen N,
- Bager CL,
- Bay-Jensen AC,
- Kehlet SN,
- Harling H,
- Leeming DJ,
- Karsdal MA,
- Jorgensen LN,
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…
Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Brix S,
- Workman CT,
- Nielsen HB,
- Christiansen C,
- Dragsbæk K,
- Neergaard JS,
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…
Journal:
Authors:
- Van Haaften WT,
- Mortensen JH,
- Karsdal MA,
- Bay-Jensen AC,
- Dijkstra G,
- Olinga P,
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…
Journal:
Authors:
- Hjuler ST,
- Gydesen S,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
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…
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,
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…
Journal:
Authors:
- Stribos EGD,
- Nielsen SH,
- Brix S,
- Karsdal MA,
- Seelen MA,
- van Goor H,
- Bakker SJL,
- Olinga P,
- Mutsaers HAM,
- Genovese F,
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…
Journal:
Authors:
- Genovese F,
- Cockwell P,
- Karsdal MA,
- Sørensen J,
- Ferro CJ,
- Jesky MD,
- Fenton A,
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 …
Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Nielsen HB,
- Brix S,
- Karsdal MA,
- Henriksen K,
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…
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,
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 …
Journal:
Authors:
- Lund A,
- Sørensen H,
- Jensen TW,
- Niemann MJ,
- Olesen ND,
- Nielsen HB,
- Olsen NV,
- Secher NH,
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…
Journal:
Authors:
- Hijmans RS,
- Rasmussen DG,
- Yazdani S,
- Navis G,
- van Goor H,
- Karsdal MA,
- Genovese F,
- van den Born J,
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 …
Journal:
Authors:
- Gydesen S,
- Andreassen KV,
- Hjuler ST,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
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 …
Journal:
Authors:
- Willumsen N,
- Bager CL,
- Leeming DJ,
- Bay-Jensen AC,
- Karsdal MA,
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 …
Journal:
Authors:
- Dragsbæk K,
- Neergaard JS,
- Christiansen C,
- Karsdal MA,
- Beck-Nielsen H,
- Brix S,
- Henriksen K,
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…
Journal:
Authors:
- Sanchez C,
- Bay-Jensen AC,
- Pap T,
- Dvir-Ginzberg M,
- Quasnichka H,
- Barrett-Jolley R,
- Mobasheri A,
- Henrotin Y,
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…
Journal:
Authors:
- Luo Y,
- Sinkeviciute D,
- He Y,
- Karsdal MA,
- Henrotin Y,
- Mobasheri A,
- Önnerfjord P,
- Bay-Jensen AC,
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…
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,
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…
Journal:
Authors:
- Montano Almendras CP,
- Thudium CS,
- Löfvall H,
- Moscatelli I,
- Schambach A,
- Henriksen K,
- Richter J,
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…
Journal:
Authors:
- Gydesen S,
- Hjuler ST,
- Freving Z,
- Andreassen KV,
- Sonne N,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
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…
Journal:
Authors:
- Arends RH,
- Karsdal MA,
- Verburg KM,
- West CR,
- Bay-Jensen AC,
- Keller DS,
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…
Journal:
Authors:
- Bihlet AR,
- Karsdal MA,
- Sand JM,
- Leeming DJ,
- Roberts M,
- Bowler R,
- White W,
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…
Journal:
Authors:
- Mobasheri A,
- Bay-Jensen AC,
- Van Spil WE,
- Larkin J,
- Levesque MC,
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…
Journal:
Authors:
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…
Journal:
Authors:
- Gudmann NS,
- Siebuhr AS,
- Christensen AF,
- Ejstrup L,
- Sørensen GL,
- Loft AG,
- Karsdal MA,
- Bay-Jensen AC,
- Munk HL,
- Junker P,