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...
September 24, 2021
Journal:
J Orthop Traumatol
Author:
Luo Y, Samuels J, Krasnokutsky S, Byrjalsen I, Kraus VB, He Y, Karsdal MA, Abramson SB, Attur M, Bay-Jensen AC
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...
September 10, 2021
Journal:
J Pharm Biomed Anal.
Author:
Reese-Petersen AL, Willumsen N, Palau P, Nunez J, Sun S, Manon-Jensen T, Kamall B, Karsdal MA, Genovese F
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...
September 5, 2021
Journal:
Aliment Pharmacol Ther.
Author:
Bjørn S Madsen, Maja Thiele, Sönke Detlefsen, Maria Kjaergaard, Linda S Møller, Jonel Trebicka, Mette J Nielsen, Natasja Stæhr Gudmann, Diana J Leeming, Karsdal MA, Aleksander Krag
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...
August 31, 2021
Journal:
Arthritis Res Ther
Author:
Jr Alexander LC, McHorse G, Huebner JL, Bay-Jensen AC, Karsdal MA, Kraus VB
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...
August 26, 2021
Journal:
J Hepatol
Author:
Juul Nielsen M, Leeming DJ, Goodman Z, Friedman S, Frederiksen P, Rasmussen KD, Vig P, Seyedkazemi S, Fischer L, Torstenson R, Karsdal MA, Lefebvre E, Sanyal JA, Ratziu V
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...
August 26, 2021
Journal:
Clin Biochem
Author:
Karsdal MA, F Genovese, Rasmussen DGK, Bay-Jensen AC, Mortensen JH, Holm Nielsen S, Willumsen N, Jensen C, Manon-Jensen T, Jennings L, Reese-Petersen AL, Henriksen K, Sand JM, Bager C, Leeming DJ
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...
August 24, 2021
Journal:
Expert Rev Mol Diagn
Author:
Pehrsson M, Mortensen JH, Manon-Jensen T, Bay-Jensen AC, Karsdal MA, Davies MJ
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...
July 29, 2021
Journal:
Osteoarthritis Cartilage
Author:
Bjerre-Bastos JJ, Nielsen HB, Andersen JR, Karsdal MA, Bay-Jensen AC, Boesen M, Mackey AL, Byrjalsen I, Bihlet AR
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...
July 20, 2021
Journal:
Cells
Author:
Yang X, Christian S Thudium, Bay-Jensen AC, Karsdal MA, van Santen J, Arden KN, Perry TA, Kluzek S
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...
July 10, 2021
Journal:
JHEP Rep
Author:
Erhardtsen E, Rasmussen DGK, Frederiksen P, Leeming DJ, Shevell D, Gluud LL, Karsdal MA, Aithal PG, Shattenberg MJ
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...
July 1, 2021
Journal:
Int J Cancer
Author:
Nissen NI, Kehlet S, Johansen AZ, Chen IM, Karsdal MA, Johansen, JS, Diab HMH, Jørgensen LN, Sun S, Manon-Jensen T, He Y, Langholm L, Willumsen N
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...
June 29, 2021
Journal:
Molecular Metabolism
Author:
K V Andreassen, A T Larsen, N Sonne, K E Mohamed, M A Karsdal, K Henriksen
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...
June 21, 2021
Journal:
Elife
Author:
M Ines Pascoal Ramos, Linjie Tian, Emma J de Ruiter, Chang Song, Ana Paucarmayta, Akashdip Singh, Eline Elshof, Saskia V Vijver, Jahangheer Shaik, Jason Bosiacki, Zachary Cusumano, Christina Jensen, Nicholas Willumsen, Morten A Karsdal, Linda Liu, Sol Langermann, Stefan Willems, Dallas Flies, Linde Meyaard
Objective: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Ind...
May 27, 2021
Journal:
Gut
Author:
Mozes EF, Lee AJ, Selvaraj AE, Jayaswal ANA, Trauner M, Boursier J, Fournier C, Staufer K, Stauber ER, Bugianesi E, Younes R, Gaia S, Lupsor-Platon M, Petta S, Shima T, Okanoue T, Mahadeva S, Eddowes PJ, Hirschfield MG, Newsome NP, Wong Wai-Sun V, Chan Wah-Keong, de Ledinghen V, Fan J, Shen F, Cobbold FJ, Kim W, Lee SM, Wiegand J, Karlas T, Yilmaz Y, Aithal PG, Palaniyappan N, Cassinotto C, Aggarwal S, Garg H, Ooi JG, Nakajima A, Yoneda M, Ziol M, Barget N, Geier A, Tuthill T, Brosnan JM, Anstee MQ, Neubauer S, Harrison AS, Bossuyt MP, Pavlides M
Background and aims: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alc...
May 13, 2021
Journal:
J Hepatol
Author:
Selvaraj AE, Mozes EF, Jayaswal ANA, Zafarmand HM, Vali Y, Lee AJ, Levick KC, Young AJL, Palaniyappan N, Liu Chang-Hai, Aithal PG, Romero-Gomez M, Brosnan JM, Tuthill AT, Anstee MQ, Neubauer S, Harrison AS, Bossuyt MP, Pavlides M
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue c...
April 22, 2021
Journal:
Rheumatol Int
Author:
Holm Nielsen S, Sardar S, Siebuhr AS, Schlemmer A, Schmidt Berg E, Bay-Jensen AC, Karsdal MA, Christensen JF, Kristensen S
The heterogeneous nature of osteoarthritis (OA) and the need to subtype patients is widely accepted in the field. The biomarker CRPM, a metabolite of C-reactive protein (CRP), is released to the circulation during inflammation. Blood CRPM levels have shown to be associated with disease activity and ...
March 22, 2021
Journal:
Sci Rep
Author:
Bay-Jensen AC, Bihlet A, Byrjalsen I, Andersen JR, Riis BJ, Christiansen C, Michaelis M, Guehring H, Ladel C, Karsdal MA
Background: Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD); no approved therapies for NASH currently exist. Pegbelfermin (PGBF), a human fibroblast growth factor 21 analog, has metabolic effects that may provide benefit for patients with NASH....
February 28, 2021
Journal:
Contemp Clin Trials
Author:
Abdelmalek MF, Charles ED, Sanyal JA, Harrison AS, Neuschwander-Tetri BA, Goodman Z, Ehman RA, Karsdal MA, Nakajima A, Du S, Tirucherai GS, Klinger GH, Mora J, Yamaguchi M, Shevell DE, Loomba R
Spondyloarthritis (SpA) is an umbrella term describing a family of chronic inflammatory rheumatic diseases. These diseases are characterised by inflammation of the axial skeleton, peripheral joints, and entheseal insertion sites throughout the body which can lead to structural joint damage includ...
January 21, 2021
Journal:
Autoimmunity
Author:
Groen SS, Sinkeviciute D, Bay-Jensen AC, Thudium CS, Thomsen SF, Schett G, Nielsen SH, Karsdal MA
A desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall sur...
January 19, 2021
Journal:
Sci Rep
Author:
Nissen NI, Kehlet S, Boisen MK, Liljefors M, Jensen C, Johansen AZ, Johansen JS, Erler JT, Mortensen JH, Høye A, Willumsen N, Karsdal MA
Objective: Associations between rheumatoid arthritis (RA) and effect of treatment at the tissue levels are poorly understood. We investigated the scope of released extracellular matrix (ECM) metabolites as a consequence of tissue remodelling in patients treated with methotrexate (MTX) and tocilizuma...
January 19, 2021
Journal:
Arthritis Res Ther
Author:
Drobinski PJ, Bay-Jensen AC, Karsdal MA, Sardar S, Siebuhr AS
A desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall sur...
January 13, 2021
Journal:
Sci Rep
Author:
Nissen NI, Kehlet S, Boisen MK, Liljefors M, Jensen C, Johansen AZ, Johansen JS, Erler JT, Karsdal MA, Mortensen JH, Høye A, Willumsen N
Spondyloarthritis (SpA) is an umbrella term describing a family of chronic inflammatory rheumatic diseases. These diseases are characterised by inflammation of the axial skeleton, peripheral joints, and entheseal insertion sites throughout the body which can lead to structural joint damage including...
January 12, 2021
Journal:
Autoimmun Rev.
Author:
Groen SS, Sinkeviciute D, Bay-Jensen AC, Thudium CS, Karsdal MA, Thomsen SF, Schett G, Holm Nielsen S
Osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, all have one clear common denominator; an altered turnover of bone. However, this may be more complex than a simple change in bone matrix and mineral turnover. While these diseases share a common tissue axis, thei...
December 21, 2020
Journal:
BMC Musculoskelet Disord.
Author:
Thudium CS, Nielsen SH, Sardar S, Mobasheri A, van Spil WE, Lories R, Henriksen K, Bay-Jensen AC, Karsdal MA.
Aim: Type VI collagen, is emerging as a signaling collagen originating from different types of fibroblasts. A specific fragment of Type VI collagen, the pro-peptide, is also known as the hormone endotrophin. We hypothesized that this fibroblast hormone would be of particular relevance in cancer ty...
December 18, 2020
Journal:
Hepatic Oncology
Author:
Diana J Leeming, Holm Nielsen S, Vongsuvanh R, Uchila R, Juul Nielsen M, Reese-Petersen AL, van der Poorten D, Eslam M, Schuppan D, Karsdal M, George J
Introduction: Metabolic-associated fatty liver disease is common, with fibrosis the major determinant of adverse outcomes. Population-based screening tools with high diagnostic accuracy for the staging of fibrosis are lacking. Methods: Three independent cohorts, 2 with both liver biopsy and liver s...
November 26, 2020
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Eslam M, Wong GL, Hashem AM, Chan HL, Nielsen MJ, Leeming DJ, Chan AW, Chen Y, Duffin KL, Schattenberg JM, George J, Wong VW, Karsdal MA
Connective tissue (ConT) remodeling is an essential process in tissue regeneration, where a balanced replacement of old tissue by new tissue occurs. This balance is disturbed in chronic diseases, often autoimmune diseases, usually resulting in the buld up of fibrosis and a gradual loss of organ func...
November 12, 2020
Journal:
Autoimmunity
Author:
Karsdal MA, Kraus VB, Shevell D, Bay-Jensen AC, Schattenberg J, Rambabu Surabattula R, Schuppan D
The effect of direct-acting antiviral (DAA) therapy on extracellular matrix (ECM) turnover, a prominent feature of chronic hepatitis C (CHC), is unknown. ECM protein degradation and formation generate fragments reflecting the tissue turnover balance when quantified in the blood. PRO-C3 and PRO-C4 re...
October 15, 2020
Journal:
J Viral Hepat
Author:
Laursen TL, Villesen IF, Leeming DJ, Karsdal MA, Sølund C, Tarp B, Kristensen LH, Holmboe CH, Leuthcher P, Laursen AL, Gudmann NS, Grønbaek H
Different stimulants might induce different extracellular matrix profiles. It is essential to gain an understanding and quantification of these changes to allow for focused anti-fibrotic drug development. This study investigated the expression of extracellular matrix by dermal fibroblast mimicking f...
October 14, 2020
Journal:
Sci Rep
Author:
Juhl P, Bondesen S, Hawkins CL, Karsdal MA, Bay-Jensen AC, Davies MJ, Siebuhr AS
Background: Tissue released blood-based biomarkers can provide insight into drug mode of action and response. To understand the changes in extracellular matrix turnover, we analyzed biomarkers associated with joint tissue turnover from a phase 3, randomized, placebo-controlled study of baricitinib i...
October 12, 2020
Journal:
Arthritis Res Ther
Author:
Thudium CS, Bay-Jensen AC, Cahya S, Dow ER, Karsdal MA, Koch AE, Zhang W, Benschop RJ
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