Sprifermin (rhFGF18) Versus Vehicle Induces a Biphasic Process of Extracellular Matrix Remodeling in Human Knee OA Articular Cartilage Ex Vivo
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…
Journal:
Authors:
- Reker D,
- Siebuhr AS,
- Thudium CS,
- Gantzel T,
- Ladel C,
- Michaelis M,
- Aspberg A,
- Berchtold MW,
- Karsdal MA,
- Gigout A,
- Bay-Jensen AC,
Sprifermin (rhFGF18) Modulates Extracellular Matrix Turnover in Cartilage Explants ex vivo
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…
Journal:
Authors:
- Reker D,
- Kjelgaard-Petersen CF,
- Siebuhr AS,
- Michaelis M,
- Gigout A,
- Karsdal MA,
- Ladel C,
- Bay-Jensen AC,
Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future
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…
Journal:
Authors:
- Karsdal MA,
- Michaelis M,
- Ladel C,
- Siebuhr AS,
- Bihlet AR,
- Andersen JR,
- Guehring H,
- Christiansen C,
- Bay-Jensen AC,
- Kraus VB,
Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort
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) i…
Journal:
Authors:
- Saberi Hosnijeh F,
- Siebuhr AS,
- Uitterlinden AG,
- Oei EH,
- Hofman A,
- Karsdal MA,
- Bierma-Zeinstra SM,
- Bay-Jensen AC,
- van Meurs JB,
Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis
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 …
Journal:
Authors:
- Bay-Jensen AC,
- Karsdal MA,
- Ladel C,
- Christiansen TG,
- Siebuhr AS,
- Kjelgaard-Petersen CF,
Sensitization and Serological Biomarkers in Knee Osteoarthritis Patients With Different Degrees of Synovitis
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.
…
Journal:
Authors:
- Petersen KK,
- Siebuhr AS,
- Graven-Nielsen T,
- Simonsen O,
- Boesen MP,
- Gudbergsen H,
- Karsdal MA,
- Bay-Jensen AC,
- Arendt-Nielsen L,
Inflammation (or synovitis)-driven osteoarthritis: an opportunity for personalizing prognosis and treatment?
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…
Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Jordan JM,
- Kjelgaard-Petersen CF,
- Christiansen C,
- Abramson SB,
- Attur M,
- Berenbaum F,
- Kraus V,
- Karsdal MA,
Association between biochemical cartilage markers and clinical symptoms in patients with hip osteoarthritis: cohort study with 2-year follow-up
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 st…
Journal:
Authors:
- Dorleijn DM,
- Luijsterburg PA,
- Bay-Jensen AC,
- Siebuhr AS,
- Karsdal MA,
- Rozendaal RM,
- Bos PK,
- Bierma-Zeinstra SM,
Association between experimental pain biomarkers and serologic markers in patients with different degrees of painful knee osteoarthritis
OBJECTIVE:
To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.
METHODS:
The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using t…
Journal:
Authors:
- Arendt-Nielsen L,
- Eskehave TN,
- Egsgaard LL,
- Petersen KK,
- Graven-Nielsen T,
- Hoeck HC,
- Simonsen O,
- Siebuhr AS,
- Karsdal MA,
- Bay-Jensen AC,
Cartilage turnover reflected by metabolic processing of type II collagen: a novel marker of anabolic function in chondrocytes
The aim of this study was to enable measurement of cartilage formation by a novel biomarker of type II collagen formation. The competitive enzyme-linked immunosorbent assay (ELISA) Pro-C2 was developed and characterized for assessment of the beta splice variant of type II procollagen (PIIBNP). This …
Journal:
Authors:
- Gudmann NS,
- Wang J,
- Hoielt S,
- Chen P,
- Siebuhr AS,
- He Y,
- Christiansen TG,
- Karsdal MA,
- Bay-Jensen AC,
Association Between Experimental Pain Biomarkers and Serological Markers in Patients With Different Degree of Painful Knee Osteoarthritis
OBJECTIVE:
To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.
METHODS:
The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using t…
Journal:
Authors:
- Arendt-Nielsen L,
- Eskehave TN,
- Egsgaard LL,
- Petersen KK,
- Graven-Nielsen T,
- Hoeck HC,
- Simonsen O,
- Siebuhr AS,
- Karsdal MA,
- Bay-Jensen AC,
Biomarkers of cartilage and surrounding joint tissue
The identification and clinical demonstration of efficacy and safety of osteo- and chondro-protective drugs are met with certain difficulties. During the last few decades, the pharmaceutical industry has, in the field of rheumatology, experienced disappointments associated with the development of di…
Journal:
Authors:
- Siebuhr AS,
- He Y,
- Gudmann NS,
- Gram A,
- Kjelgaard-Petersen CF,
- Qvist P,
- Karsdal MA,
- Bay-Jensen AC,
The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases
BACKGROUND:
Matrix metalloproteinase-3 (MMP-3) plays an important role in the pathology of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Measurement of active MMP-3 in clinical samples could provide information about progression of rheumatoid diseases, and potentially response to treat…
Journal:
Authors:
- Sun S,
- Bay-Jensen AC,
- Karsdal MA,
- Siebuhr AS,
- Zheng Q,
- Maksymowych WP,
- Christiansen TG,
- Henriksen K,
Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover
OBJECTIVES:
Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive C…
Journal:
Authors:
- Siebuhr AS,
- Petersen KK,
- Arendt-Nielsen L,
- Egsgaard LL,
- Eskehave T,
- Christiansen C,
- Simonsen O,
- Hoeck HC,
- Karsdal MA,
- Bay-Jensen AC,
Serological identification of fast progressors of structural damage with rheumatoid arthritis
INTRODUCTION:
Rheumatoid arthritis (RA) patients with structural progression are in most need of immediate treatment to maintain tissue integrity. The serum protein fingerprint, type I collagen degradation mediated by matrix metalloproteinases (MMP)-cleavage (C1M), is a biomarker of tissue destruct…
Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Leeming DJ,
- Plat A,
- Byrjalsen I,
- Christiansen C,
- van de Heijde D,
- Karsdal MA,