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
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
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
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
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
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
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, Zegzulkova K, Tomcik M, Bubová K, Horínková J, Gatterová J, Pavelka K, Siebuhr AS, Forejtová S, Gregová S
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
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, Zegzulkova K, Tomcik M, Urbanova M, Grobelna K, Gatterova J, Bay-Jensen AC, Pavelka K, Forejtová S
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 JC
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
BACKGROUND: Radiographic axial spondyloarthritis (r-axSpA) is associated with extracellular matrix (ECM) remodelling of affected tissues. We investigated whether there was a relationship between biomarkers of ECM remodelling and 2-year radiographic progression in r-axSpA. METHODS: Patients from the...
May 14, 2018
Journal:
RMD open
Author:
Siebuhr AS, van de Heijde D, Bay-Jensen AC, Karsdal MA, Landewé R, van Tubergen A, Ramiro S
OBJECTIVES: The expanding spectrum of targeted therapies for rheumatoid arthritis (RA) implies a need for development of precision tools for disease assessment reflecting pathobiologic processes. Type IV collagen is an abundant protein of basement membranes, but is also present in the intercellular ...
May 8, 2018
Journal:
Clin Exp Rheumatol
Author:
Gudmann NS, Junker P, Juhl P, Thudium CS, Siebuhr AS, Byrjalsen I, Karsdal MA, Bay-Jensen AC
Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients wi...
March 1, 2018
Journal:
Assay Drug Dev Technol
Author:
Lamy P, Juhl P, Siebuhr AS, Iversen LV, Nawrocki A, Larsen MR, Domsic RT, Franchimont N, Karsdal MA, Leeming DJ, Chavez JC, Bülow Sand JM
OBJECTIVES: The objective of this study was to examine the tissue degradation in response to anti-IL6 receptor treatment in rheumatoid arthritis (RA) patients which are anti-TNF-α inadequate responders. METHODS: RADIATE was a randomised, double-blinded, placebo-controlled, parallel-group, phase III...
January 31, 2018
Journal:
Clin Exp Rheumatol
Author:
Juhl P, Thudium CS, Gudmann NS, Karsdal MA, Bay-Jensen AC, Siebuhr AS
BACKGROUND: Sprifermin (recombinant human fibroblast growth factor 18) is in clinical development as a potential disease-modifying osteoarthritis drug (DMOAD). In vitro studies have shown that cartilage regenerative properties of sprifermin involve chondrocyte proliferation and extracellular matrix ...
December 12, 2017
Journal:
J Transl Med
Author:
Reker D, Kjelgaard-Petersen CF, Siebuhr AS, Michaelis M, Gigout A, Karsdal MA, Ladel C, Bay-Jensen AC
The objective of this study was to investigate the patient-reported outcomes (PROs) and matrix metalloproteinase (MMP) derived extracellular matrix (ECM) biomarkers in non-radiographic (nr)-axial spondyloarthritis (axSpA) and radiographic (r)-axSpA after exercise intervention. Forty-six axSpA patien...
August 30, 2017
Journal:
Clin Rheumatol.
Author:
Husakova M, Siebuhr AS, Pavelka K, Spiritovic M, Bay-Jensen AC, Levitova A
OBJECTIVE: Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a comm...
August 28, 2017
Journal:
Clin Exp Rheumatol
Author:
Siebuhr AS, Kjelgaard-Petersen CF, Sun S, Byrjalsen I, Christiansen C, Karsdal MA, Bay-Jensen AC
Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or...
July 21, 2017
Journal:
Adv Drug Deliv Rev
Author:
Karsdal MA, Nielsen SH, Leeming DJ, Langholm LL, Nielsen MJ, Manon-Jensen T, Siebuhr AS, Gudmann NS, Rønnow S, Daniels SJ, Mortensen JH, Schuppan D, Bülow Sand JM
Objectives: To investigate the turnover of type I and III collagen by neo-epitope markers in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Methods: Patients with PsA (n=101) or axSpA (n=110) and healthy subjects (n=120) were included. Demographic and clinical data wer...
January 5, 2017
Journal:
Clin Exp Rheumatol
Author:
Gudmann NS, Siebuhr AS, Christensen AF, Ejstrup L, Sørensen GL, Loft AG, Karsdal MA, Bay-Jensen AC, Munk HL, Junker P
Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying t...
August 2, 2016
Journal:
Osteoarthritis Cartilage
Author:
Karsdal MA, Michaelis M, Ladel C, Siebuhr AS, Bihlet AR, Andersen JR, Guehring H, Christiansen C, Bay-Jensen AC, Kraus VB
BACKGROUND: Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. Th...
June 16, 2016
Journal:
Arthritis Res Ther
Author:
Gudmann NS, Munk HL, Christensen AF, Ejstrup L, Sørensen GL, Loft AG, Karsdal MA, Bay-Jensen AC, He Y, Siebuhr AS, Junker P
OBJECTIVE: Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares. METHODS: Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples from...
June 2, 2016
Journal:
Rheumatology (Oxford)
Author:
Valdes AM, Manon-Jensen T, Abhishek A, Jenkins W, Siebuhr AS, Karsdal MA, Doherty S, Zhang W, Richardson H, Doherty M, Bay-Jensen AC
BACKGROUND: We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) in...
April 1, 2016
Journal:
Arthritis Res Ther
Author:
Saberi Hosnijeh F, Siebuhr AS, Uitterlinden AG, Oei EH, Hofman A, Karsdal MA, Bierma-Zeinstra SM, Bay-Jensen AC, van Meurs JB
OBJECTIVE: Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium. METHODS: Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in the co...
February 10, 2016
Journal:
Biomarkers
Author:
Bay-Jensen AC, Karsdal MA, Ladel C, Christiansen TG, Siebuhr AS, Kjelgaard-Petersen CF
OBJECTIVE:Synovitis is a frequent condition in knee osteoarthritis (KOA) and has been associated with pain. This study investigated the links between the pressure hyperalgesia, the clinical pain, the degree of the synovitis, inflammatory biomarkers, and tissue-specific biomarkers in KOA patients. M...
December 2, 2015
Journal:
Clin J Pain
Author:
Petersen KK, Siebuhr AS, Graven-Nielsen T, Simonsen O, Boesen MP, Gudbergsen H, Karsdal MA, Bay-Jensen AC, Arendt-Nielsen L
The disabling and painful disease osteoarthritis (OA) is the most common form of arthritis. Strong evidence suggests that a subpopulation of OA patients has a form of OA driven by inflammation. Consequently, understanding when inflammation is the driver of disease progression and which OA patients m...
October 20, 2015
Journal:
Scand J Rheumatol
Author:
Siebuhr AS, Bay-Jensen AC, Jordan JM, Kjelgaard-Petersen CF, Christiansen C, Abramson SB, Attur M, Berenbaum F, Kraus VB, Karsdal MA
Objectives: To assess associations between uCTX-II or uCIIM and severity of hip pain in patients with mild-moderate hip osteoarthritis (OA) over a 2-year period, and establish whether the level of these biomarkers at baseline could estimate a specific trajectory of hip pain. Design: A cohort study ...
January 1, 2015
Journal:
Osteoarthritis Cartilage
Author:
Dorleijn DM, Luijsterburg PA, Bay-Jensen AC, Siebuhr AS, Karsdal MA, Rozendaal RM, Bos PK, Bierma-Zeinstra SM
Background and aim: Alkaptonuria (AKU) clinical manifestations resemble severe arthritis. The Suitability of Nitisinone in Alkaptonuria 1 (SONIA 1) study is a dose-finding trial for nitisinone treatment of AKU patients. We tested a panel of serum and urinary biomarkers reflecting extracellular matri...
January 1, 2015
Journal:
JIMD Rep
Author:
Genovese F, Siebuhr AS, Musa K, Gallagher JA, Milan AM, Karsdal MA, Rovensky J, Bay-Jensen AC, Ranganath LR
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