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
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
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 ...
Introduction: Extracellular matrix (ECM) remodeling of the intestinal tissue is important in inflammatory bowel disease (IBD) due to the extensive mucosal remodeling. There are still gaps in our knowledge as to how ECM remodeling is related to intestinal epithelium homeostasis and healing of the int...
October 22, 2019
Journal:
Expert Rev Gastroenterol Hepatol
Author:
Mortensen JH, Lindholm M, Langholm LL, Kjeldsen J, Bay-Jensen AC, Karsdal MA, Manon-Jensen T
Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th...
Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th...
Background: Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee jo...
September 3, 2019
Journal:
Arthritis Res Ther
Author:
Bihlet AR, Byrjalsen I, Bay-Jensen AC, Andersen JR, Christiansen C, Riis BJ, Karsdal MA
BACKGROUND: Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee jo...
September 3, 2019
Journal:
Arthritis Res Ther
Author:
Bihlet AR, Byrjalsen I, Bay-Jensen AC, Andersen JR, Christiansen C, Riis BJ, Karsdal MA
Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A...
August 2, 2019
Journal:
Sci Rep
Author:
Husakova M, Bay-Jensen AC, forejtová S, Zegzulkova K, Tomcik M, gregová M, Bubová K, Horínková J, Gatterová J, Pavelka K, Siebuhr AS
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...
BACKGROUND: Osteoarthritis (OA) leads to joint failure and total joint replacement (TJR, either hip (H) or knee (K)). Worsening of pain and joint space narrowing are believed to be surrogates for joint failure; however, we hypothesize that TJR, as a reflection of joint failure, can be used as an end...
June 26, 2019
Journal:
BMC Musculoskelet Disord
Author:
Bager CL, Karsdal MA, Bihlet A, Thudium CS, Byrjalsen I, Bay-Jensen AC
BACKGROUND AND AIMS: Crohns disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formati...
June 1, 2019
Journal:
J Gastrointestin Liver Dis
Author:
Sun S, Karsdal MA, Mortensen JH, Luo Y, Kjeldsen J, Krag A, Jensen MD, Bay-Jensen AC, Manon-Jensen T
OBJECTIVE: The objective was to investigate blood-based biomarkers of type I (PRO-C1), III (PRO-C3) and VI (PRO-C6) collagen formation in systemic sclerosis (SSc) patients and examine their correlation to modified Rodnan skin score (mRSS). METHODS: Limited (lSSc, n = 76) and diffuse SSc (dSSc, n = 4...
March 1, 2019
Journal:
Biomarkers
Author:
Juhl P, Vinderslev Iversen L, Karlsmark T, Karsdal MA, Bay-Jensen AC, Mogensen M, Siebuhr AS
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