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
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
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
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
C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe...
February 28, 2019
Journal:
Sci Rep
Author:
Löfvall H, Katri A, Dabrowska A, Karsdal MA, Luo Y, He Y, Manon-Jensen T, Dziegiel MH, Bay-Jensen AC, Thudium CS, Henriksen K
OBJECTIVES: Non-radiographic (nr-axSpA) and radiographic (AS) forms of axial spondyloarthritis (axSpA) share clinical features, but have different radiographic patterns. Radiographic progression is not associated with the current disease activity biomarkers. We investigated a matrix metalloproteinas...
February 11, 2019
Journal:
Clin Exp Rheumatol
Author:
Siebuhr AS, Husakova M, forejtová S, Zegzulkova K, Tomcik M, Urbanova M, Grobelna K, Gatterova J, Bay-Jensen AC, Pavelka K
Background: Crohn’s disease (CD) is a chronic inflammatory condition of the intestinal tract resulting in severe intestinal tissue damage. The concept of mucosal healing has therefore gained significant interest as a therapeutic end point in the treatment of inflammatory bowel disease (IBD). Given t...
January 31, 2019
Journal:
EC Gastroenterology and Digestive
Author:
Manon-Jensen T, Langholm LL, Sun S, Mortensen JH, He Y, Krag A, Jensen MD, Bay-Jensen AC, Kjeldsen J, Karsdal MA
PURPOSE OF REVIEW: This review focuses on the molecular taxonomy of osteoarthritis from the perspective of molecular biomarkers. We discuss how wet biochemical markers may be used to understand disease pathogenesis and progression and define molecular endotypes of osteoarthritis and how these corres...
January 31, 2019
Journal:
Curr Opin Rheumatol
Author:
mobasheri A, Van Spil WE, Budd E, Uzieliene I, Bernotiene E, Bay-Jensen AC, Larkin J, Levesque MC, Gualillo O, Henrotin Y
OBJECTIVE: Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of OA, of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type X collagen to...
January 14, 2019
Journal:
Osteoarthritis Cartilage
Author:
He Y, Manon-Jensen T, Arendt-Nielsen L, Petersen KK, Christiansen T, Samuels J, Abramson S, Karsdal MA, Attur M, Bay-Jensen AC
There is a need for efficacious and safe pain treatments for OA (osteoarthritis). The nerve growth factor (NGF) antibody tanezumab is associated with high efficacy, but when combined with chronic NSAID treatment shows an increased risk of rapidly progressive osteoarthritis (RPOA) in a small group of...
December 18, 2018
Journal:
Osteoarthritis Cartilage
Author:
Karsdal MA, Verburg KM, West CR, Bay-Jensen AC
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 th...
December 3, 2018
Journal:
PLoS One
Author:
Juhl P, Bay-Jensen AC, Karsdal MA, Siebuhr AS, Franchimont N, Chavez J
PURPOSE: Extracellular matrix (ECM) deposition and remodelling in skin and lungs of systemic sclerosis (SSc) subjects lead to release of metabolites/biomarkers into circulation. We investigated if biomarkers of ECM degradation (biglycan and elastin) and macrophage activation (citrullinated vimentin)...
November 20, 2018
Journal:
Biomarkers
Author:
Siebuhr AS, Juhl P, Bay-Jensen AC, Karsdal MA, Franchimont N, Chavez JC
N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH₂-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utili...
November 6, 2018
Journal:
Int J Mol Sci
Author:
Luo Y, He Y, Gudmann NS, Henriksen K, Simonsen O, Ladel C, Michaels M, Mobasheri A, Karsdal MA, Bay-Jensen AC
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