A dual role for UCMA in osteoarthritis-Inhibition of aggrecanases and promotion of bone turnover

Stock M, Menges S, Eitzinger N, Gesslein M, Botschner R, Wormser L, Distler A, Schlötzer-Schrehardt U, Dietel K, Distler J, Beyer C, Gelse K, Engelke K, Koenders MI, Van Den Berg W, Mark K, Schett G (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Arthritis and Rheumatology Wiley

DOI: 10.1002/art.40042

Abstract

Cartilage damage and subchondral bone changes are closely connected in osteoarthritis. How these processes are interlinked is however incompletely understood to date. Here, we investigate the mechanistic role of the cartilage-derived protein UCMA in osteoarthritis-related cartilage and bone changes.UCMA expression was assessed in healthy and osteoarthritic human and mouse cartilage. DMM-induced osteoarthritis was performed in WT and Ucma-deficient mice analysing cartilage and bone changes. UCMA-collagen interactions, effect of UCMA on aggrecanase activity and the impact of recombinant UCMA on osteoclast differentiation were studied in vitro.UCMA was found overexpressed in human and mouse osteoarthritic cartilage. DMM-triggered cartilage changes were aggravated in Ucma-deficient mice compared to WT littermates, showing increased structural damage, proteoglycan loss and chondrocyte cell death indicating chondroprotective effects of UCMA. Moreover, UCMA inhibited ADAMTS-dependent aggrecanase activity and directly interacted with cartilage-specific collagen types. In contrast, osteoarthritis-related bone changes were significantly reduced in Ucma-deficient mice, showing less pronounced osteophyte formation and subchondral bone sclerosis. Mechanistically, UCMA directly promoted osteoclast differentiation in vitro.UCMA links cartilage with bone changes in osteoarthritis, supporting cartilage integrity as an endogenous inhibitor of aggrecanases on the one hand, and promoting osteoclastogenesis and subchondral bone turnover on the other hand. Hence, UCMA represents an important link between cartilage and bone in osteoarthritis. This article is protected by copyright. All rights reserved.

Authors with CRIS profile

Michael Stock Department of Medicine 3 – Rheumatology and Immunology Stefanie Menges Professur für Molekulare Neurologie Nicole Eitzinger Medizinische Fakultät Ursula Schlötzer-Schrehardt Medizinische Fakultät Jörg Distler Professur für Molekulare Mechanismen der Organfibrose Christian Beyer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Klaus Engelke Lehrstuhl für Medizinische Physik und Mikrogewebetechnik Klaus von der Mark Medizinische Fakultät Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

Radboud University Nijmegen NL Netherlands (NL)

How to cite

APA:

Stock, M., Menges, S., Eitzinger, N., Gesslein, M., Botschner, R., Wormser, L.,... Schett, G. (2017). A dual role for UCMA in osteoarthritis-Inhibition of aggrecanases and promotion of bone turnover. Arthritis and Rheumatology. https://doi.org/10.1002/art.40042

MLA:

Stock, Michael, et al. "A dual role for UCMA in osteoarthritis-Inhibition of aggrecanases and promotion of bone turnover." Arthritis and Rheumatology (2017).

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