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
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
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
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
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
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
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.
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
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
Osteoarthritis (OA) is associated with cartilage breakdown, brought about by ADAMTS-5 mediated aggrecan degradation followed by MMP-derived aggrecan and type II collagen degradation. We investigated a novel anti-ADAMTS-5 inhibiting Nanobody® (M6495) on cartilage turnover ex vivo. Bovine cartilage (B...
September 20, 2020
Journal:
Int J Mol Sci
Author:
Siebuhr AS, Wekman D, Bay-Jensen AC, Thudium CS, Karsdal MA, Serruys B, Ladel C, Michaelis M, Lindemann S
Objective: Dysregulation of type I collagen metabolism has a great impact on human health. We have previously seen that matrix metalloproteinase-degraded type I collagen (C1M) is associated with early death and age-related pathologies. To dissect the biological impact of type I collagen dysregulatio...
September 20, 2020
Journal:
Neurol Genet
Author:
Tang ME, Blair JPM, Bager CL, Bay-Jensen AC, Henriksen K, Christiansen C, Karsdal MA.
Introduction: Anti-tumor necrosis factor (TNF) therapy is effective in inducing remission in Crohn's disease in 60% of patients. No serological biomarkers are available, which can predict response to anti-TNF. We aimed to investigate serological markers of collagen turnover reflecting tissue inflamm...
September 11, 2020
Journal:
Clin Transl Gastroenterol
Author:
van Haaften WT, Mortensen JH, Dige AK, Grønbæk H, Hvas CL, Bay-Jensen AC, Karsdal MA, Olinga P, Manon-Jensen T, Dijkstra G
Introduction: Anti-tumor necrosis factor (TNF) therapy is effective in inducing remission in Crohn's disease in 60% of patients. No serological biomarkers are available, which can predict response to anti-TNF. We aimed to investigate serological markers of collagen turnover reflecting tissue inflamm...
September 11, 2020
Journal:
Clin Transl Gastroenterol
Author:
van Haaften WT, Mortensen JH, Dige AK, Grønbæk H, Hvas CL, Bay-Jensen AC, Karsdal MA, Olinga P, Manon-Jensen T, Dijkstra G
Introduction: Anti-tumor necrosis factor (TNF) therapy is effective in inducing remission in Crohn's disease in 60% of patients. No serological biomarkers are available, which can predict response to anti-TNF. We aimed to investigate serological markers of collagen turnover reflecting tissue inflamm...
September 11, 2020
Journal:
Clin Transl Gastroenterol
Author:
van Haaften WT, Mortensen JH, Dige AK, Grønbæk H, Hvas CL, Bay-Jensen AC, Karsdal MA, Olinga P, Manon-Jensen T, Dijkstra G
Rheumatoid arthritis (RA) is a chronic inflammatory disease with fluctuating course of progression. Despite substantial improvement in treatments in recent years, treatment response is still not guaranteed. The aim of this study was to identify variation in Disease Activity Score 28 (DAS28) of RA pa...
August 18, 2020
Journal:
Sci Rep
Author:
Blair JPM, Bay-Jensen AC, Thang MH, Frederiksen P, Bager C, Karsdal MA, Brunak S
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...
May 12, 2020
Journal:
BMC Rheumatol
Author:
Sinkeviciute D, Aspberg A, He Y, Bay-Jensen AC, Önnerfjord P
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...
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, e...
April 23, 2020
Journal:
Int J Rheum Dis
Author:
Kubo S, Siebuhr AS, Bay-Jensen AC, Juhl P, Karsdal MA, Satoh Y, Todoroki Y, Nakano K, Nakayamada S, Tanaka Y
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 wheth...
April 14, 2020
Journal:
J Clin Gastroenterol
Author:
Mortensen JH, Van Haaften WT, Karsdal MA, Bay-Jensen AC, Olinga P, Grønbæk H, Hvas CL, Manon-Jensen T, Dijkstra G, Dige A
Background: Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable effo...
April 7, 2020
Journal:
Dis Markers.
Author:
Veidal SS, Bay-Jensen AC, Tougas G, Vainer B, Morten A Karsdal
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...
April 7, 2020
Journal:
Sci Rep
Author:
Reker D, Siebuhr AS, Thudium CS, Gantzel T, Ladel C, Michaelis M, Aspberg A, Berchtold MW, Karsdal MA, Gigout A, Bay-Jensen AC
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...
March 15, 2020
Journal:
Semin Arthritis Rheum
Author:
Bihlet A, Bjerre-Bastos JJ, Andersen JR, Byrjalsen I, Karsdal MA, Bay-Jensen AC
Objective: Links between pain and joint degradation are poorly understood. We investigated the role of activation of Toll-like receptors (TLR) by cartilage metabolites in initiating and maintaining the inflammatory loop in OA causing joint destruction. Methods: Synovial membrane explants (SMEs) wer...
November 14, 2019
Journal:
Osteoarthritis Cartilage
Author:
Sharma N, drobinski P, Kayed A, Chen Z, Kjelgaard-Petersen CF, Gantzel T, Karsdal MA, Michaels M, Ladel C, Bay-Jensen AC, Lindemann S, Thudium CS
Ex vivo culture systems cover a broad range of experiments dedicated to studying tissue and cellular function in a native setting. Cartilage is a unique tissue important for proper function of the synovial joint and is constituted by a dense extracellular matrix (ECM), rich in proteoglycan and type ...
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