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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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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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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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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,
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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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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Authors:

  • Holm Nielsen S,
  • guldager Kring Rasmussen D,
  • Brix S,
  • Jesky M,
  • Fenton A,
  • Ferro CJ,
  • Karsdal MA,
  • Genovese F,
  • Cockwell P,
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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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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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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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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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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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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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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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,
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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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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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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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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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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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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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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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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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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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,
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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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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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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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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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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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,
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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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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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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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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