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The activation fragment of PAR2 is elevated in serum from patients with rheumatoid arthritis and reduced in response to anti-IL6R treatment.

December 20, 2021

Sci Rep

Abstract Osteoarthritis (OA) and rheumatoid arthritis (RA) are serious and painful diseases. Protease-activated receptor 2 (PAR2) is involved in the pathology of both OA and RA including roles in synovial hyperplasia, cartilage destruction, osteophyogenesis and pain. PAR2 is activated via cleavage of its N-terminus by serine proteases. In this study a competitive ELISA assay was […]

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The Anti-ADAMTS-5 Nanobody(®) M6495 Protects Cartilage Degradation Ex Vivo.

August 20, 2020

Int J Mol Sci

Abstract 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 (BEX, = 4), human osteoarthritic – (HEX, = 8) and healthy-cartilage (hHEX, = 1) explants and […]

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Inflammation and joint destruction may be linked to the generation of cartilage metabolites of ADAMTS-5 through activation of toll-like receptors.

May 1, 2020

Osteoarthritis Cartilage

Abstract 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) were prepared from OA patients’ synovial biopsies. SMEs were cultured for 10 days under […]

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Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII-deficient mice.

November 1, 2019

J Thromb Haemost

Abstract BACKGROUND Vascular remodeling associated with hemophilic arthropathy (HA) may contribute to bleed propagation, but the mechanisms remain poorly understood. OBJECTIVES To explore molecular mechanisms of HA and the effects of hemostasis correction on synovial vascular remodeling after joint injury in hypocoagulable mice. METHODS Factor VIII (FVIII)-deficient mice +/- FVIII treatment and hypocoagulable wild-type mice […]

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Biochemical markers in osteoarthritis with lessons learned from osteoporosis.

October 1, 2019

Clin Exp Rheumatol

Abstract 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 the projects with the highest chance of success. Biomarkers for […]

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Type IV collagen metabolism is associated with disease activity, radiographic progression and response to tocilizumab in rheumatoid arthritis.

October 1, 2018

Clin Exp Rheumatol

Abstract 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 matrix of the synovial lining layer. We aimed to investigate the association […]

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Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis.

September 1, 2018

Arthritis Rheumatol

Abstract OBJECTIVE Rheumatoid arthritis (RA) is a chronic and degenerative autoimmune joint disease that leads to disability, reduced quality of life, and increased mortality. Although several synthetic and biologic disease-modifying antirheumatic drugs are available, there is still a medical need for novel drugs that control disease progression. As only 10% of experimental drug candidates for […]

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Increased remodelling of interstitial collagens and basement membrane is suppressed by treatment in patients with rheumatoid arthritis: serological evaluation of a one-year prospective study of 149 Japanese patients.

June 1, 2018

Clin Exp Rheumatol

Abstract OBJECTIVES This prospective study aimed to use serological biomarkers for evaluation of, connective tissue turnover, in a population of 149 Japanese patients with rheumatoid arthritis (RA). It was aimed to investigate how the connective tissue was affected by treatment at follow-up after 1 year (+/- 6 weeks) with either methotrexate (n=23) alone, or in […]

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Development and use of biochemical markers in osteoarthritis: current update.

January 1, 2018

Curr Opin Rheumatol

Abstract PURPOSE OF REVIEW There is an increasing demand for noninvasive and descriptive biochemical markers (biomarkers) in osteoarthritis; for enabling early drug development (including translational research), evaluating clinical trial at an early stage and for subtyping. Purpose of the review is to review and comment on current availability of such biomarkers. RECENT FINDINGS Many different […]

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Altered collagen turnover in factor VIII-deficient rats with hemophilic arthropathy identifies potential novel serological biomarkers in hemophilia.

December 1, 2016

J Thromb Haemost

Abstract UNLABELLED Essentials Joint bleeding in hemophilia may induce significant remodeling of the extracellular matrix. Biomarkers of collagen turnover were investigated in a F8 rat model of hemophilic arthropathy. Biomarkers of cartilage degradation increased significantly during development of arthropathy. Basement membrane and interstitial matrix turnover changed significantly following hemarthrosis. SUMMARY Background Hemophilic arthropathy is a […]

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