Promising targets for therapy of osteoarthritis: a review on the Wnt and TGF-β signalling pathways.

Autor:	Cherifi C; Department of Development and Regeneration, KU Leuven, Skeletal Biology and Engineering Research Centre, Leuven, Belgium., Monteagudo S; Department of Development and Regeneration, KU Leuven, Skeletal Biology and Engineering Research Centre, Leuven, Belgium., Lories RJ; Department of Development and Regeneration, KU Leuven, Skeletal Biology and Engineering Research Centre, Box 813 O&N, Herestraat 49, Leuven 3000, Belgium; Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in musculoskeletal disease [Ther Adv Musculoskelet Dis] 2021 Apr 16; Vol. 13, pp. 1759720X211006959. Date of Electronic Publication: 2021 Apr 16 (Print Publication: 2021).
DOI:	10.1177/1759720X211006959
Abstrakt:	Osteoarthritis (OA) is the most common chronic joint disorder worldwide, with a high personal burden for the patients and an important socio-economic impact. Current therapies are largely limited to pain management and rehabilitation and exercise strategies. For advanced cases, joint replacement surgery may be the only option. Hence, there is an enormous need for the development of effective and safe disease-modifying anti-OA drugs. A strong focus in OA research has been on the identification and role of molecular signalling pathways that contribute to the balance between anabolism and catabolism in the articular cartilage. In this context, most insights have been gained in understanding the roles of the transforming growth factor-beta (TGF-β) and the Wingless-type (Wnt) signalling cascades. The emerging picture demonstrates a high degree of complexity with context-dependent events. TGF-β appears to protect cartilage under healthy conditions, but shifts in its receptor use and subsequent downstream signalling may be deleterious in aged individuals or in damaged cartilage. Likewise, low levels of Wnt activity appear important to sustain chondrocyte viability but excessive activation is associated with progressive joint damage. Emerging clinical data suggest some potential for the use of sprifermin, a recombinant forms of fibroblast growth factor 18, a distant TGF-β superfamily member, and for lorecivivint, a Wnt pathway modulator. Competing Interests: Conflict of interest statement: No funding or sponsorship was received for this study or publication of this article. Leuven Research and Development, the technology transfer office of KU Leuven has received consultancy and speaker’s fees, and research grants on behalf of Rik Lories from Abbvie, Boehringer-Ingelheim, Celgene, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Samumed and UCB. Academic research in the Lories & Monteagudo laboratory is supported by FWO Vlaanderen (Flanders Research Foundation), KU Leuven, the Excellence of Science initiative of the Federal Government, the EU H2020 and IMI2 program, Foreum and the VIB-Grand Challenges Program. (© The Author(s), 2021.)
Databáze:	MEDLINE
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