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BACKGROUND Endotrophin, a collagen type VI–derived peptide, mediates metabolic dysregulation, inflammation, and fibrosis in animal models, but has not been studied in human heart failure (HF). METHODS We examined the association between circulating endotrophin and outcomes in participants sufferi...

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Background Aberrant extracellular matrix (ECM) deposition and remodelling is important in the disease pathogenesis of pulmonary fibrosis (PF). We characterised neoepitope biomarkers released by ECM turnover in lung tissue from bleomycin-treated rats and patients with PF and analysed the effects of ...

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Background and aims: Liver fibrosis results from a prolonged wound healing response to continued injury with excessive production of extracellular proteins. In patients with chronic liver disease, the monitoring of liver fibrosis dynamics is of high interest. Whilst markers of fibrogenesis exist, ...

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Background and aims Endoscopy and the use of fecal calprotectin (fecal CP) are among the least favored methods for assessing disease activity by inflammatory bowel disease (IBD) patients; the handling/processing of fecal samples is also impractical. Therefore, we sought to develop a novel neo-epi...

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Background: Extensive extracellular matrix (ECM) remodeling is a hallmark of metastatic pancreatic ductal adenocarcinoma (mPDA). We investigated fragments of collagen types III (C3M, PRO-C3), VI (PRO-C6), and VIII (C8-C), and versican (VCANM) in plasma as biomarkers for predicting progression-free s...

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Background: Osteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilag...

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Objective: The purpose of this overview of osteoarthritis (OA) biomarkers is to provide the non-specialist with a toolbox, based on experience acquired by biomarker researchers over many years, to understand biomarkers in general and their use in the OA field. Methods: We provide an update on this ...

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September 15, 2021

Journal:
Osteoarthritis Cartilage

Author:
Kraus VB, Karsdal MA

Increased turnover of extracellular matrix proteins is seen in many different diseases and is an underlying and driving feature of pathogenesis. An increased ratio of formation over degradation of extracellular matrix proteins, such as collagens, leads to accumulation of proteins in the tissues, ult...

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Abstract Background: Alcohol is a main cause of preventable deaths and frequently leads to the development of alcohol-related liver disease. Due to the lack of diagnostics, patients are commonly diagnosed after developing clinical manifestations. Recently, the biomarker PRO-C3 was shown to accura...

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Objective: To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. Methods: Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent kn...

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Background & aims: Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder with non-alcoholic steatohepatitis (NASH) being a more progressive phenotype associated with progression to cirrhosis. Type III collagen is a main component of the fibrotic extracellular matrix. PRO-C3 is a b...

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Objectives: There is a need for precision medicine and an unspoken promise of an optimal approach for identification of the right patients for value-based medicine based on big data. However, there may be a misconception that measurement of proteins is more valuable than measurement of fewer selecte...

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Background: Liver fibrosis accumulation is considered a turnover disease, with formation exceeding degradation, although this hypothesis has never been tested in humans. Aims: To investigate extracellular matrix (ECM) remodelling in a biopsy-controlled study of alcohol-related liver disease (ALD) p...

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Introduction: Enzymatic cross-linking of the collagens within the extracellular matrix (ECM) catalyzed by enzymes such as lysyl oxidase (LOX) and lysyl oxidase like-enzymes 1-4 (LOXL), transglutaminase 2 (TG2), and peroxidasin (PXDN) contribute to fibrosis progression through extensive collagen cros...

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Objective: To investigate acute changes in biochemical markers of cartilage turnover in response to moderate intensity exercise with and without joint impact in humans with knee osteoarthritis. Design: We conducted a randomized, cross-over, exploratory clinical study. Twenty subjects with knee osteo...

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Abstract Background: Asthma is a heterogeneous syndrome substantiating the urgent requirement for endotype-specific biomarkers. Dysbalance of fibrosis and fibrolysis in asthmatic lung tissue leads to reduced levels of the inflammation-protective collagen 4 (COL4A3). Objective: To delineate the degra...

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The pathogenesis of psoriatic arthritis (PsA) involves inflammation and bone and soft tissue turnover. Dietary fatty acids have previously been associated with pro-inflammatory effects induced by saturated fatty acids (SFA) and anti-inflammatory effects achieved by at least some polyunsaturated fatt...

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To investigate the association between markers of synovial inflammation and matrix turnover (MRI-based and serum biomarkers) and knee symptoms in established knee osteoarthritis (KOA). This cross-sectional study utilised data from a randomised, multicentre placebo-controlled trial (UK-VIDEO) of vita...

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Abstract In inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with pathophysiological changes in Crohn's disease ...

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Abstract Background: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable informa...

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Background & aims: Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical...

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Type XI collagen has been associated with tumor fibrosis and aggressiveness in patients with pancreatic ductal adenocarcinoma (PDAC). The propeptide on Type XI collagen is released into the circulation after proteolytic processing at either amino acid 253 or 511. This allows for a noninvasive biomar...

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Abstract Objective: Dual amylin and calcitonin receptor agonists (DACRAs) are novel therapeutic agents that not only improve insulin sensitivity but also work as an adjunct to established T2DM therapies. DACRAs are currently administered once daily, though it is unknown whether DACRAs with increa...

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Abstract Purpose: To investigate acute changes in biochemical markers of bone and cartilage turnover in response to moderate intensity exercise with and without joint impact in healthy human subjects. Methods: A randomized, cross-over, exploratory, clinical study was conducted. Twenty healthy subjec...

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Abstract Collagens are a primary component of the extracellular matrix and are functional ligands for the inhibitory immune receptor leukocyte-associated immunoglobulin-like receptor (LAIR)-1. LAIR-2 is a secreted protein that can act as a decoy receptor by binding collagen with higher affinity t...

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Abstract Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemi...

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Background The signalling peptide endotrophin is derived through proteolytic cleavage of the carboxyl-terminal during formation of type VI collagen. It is expressed by most descendants of the mesenchymal stem cells lineage, including adipocytes and fibroblasts, and have been proposed to be a centra...

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Introduction: Interstitial, cartilage, and bone collagens have been proposed as biomarkers of joint deterioration in hemophilic arthropathy. The role of basement membrane (type IV and VIII) collagens as biomarkers of endothelial turnover in relation to acute joint bleeding is not understood. Method...

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There is a need for antidiabetic agents successfully targeting insulin sensitivity and treating obesity control at the same time. The aim of this first-in-human study was (a) to evaluate safety and tolerability, (b) to evaluate pharmacokinetics and (c) to assess indications of receptor engagement of...

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