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Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast‐derived ADAMTS‐7 and ‐12

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Pérez García, Selene and Carrión Caballo, Mar and Villanueva Romero, Raúl and Hermida Gómez, Tamara and Fernández Moreno, Mercedes and Mellado, Mario and Blanco, Francisco J. and Juarranz Moratilla, Yasmina and Gomáriz, Rosa P. (2019) Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast‐derived ADAMTS‐7 and ‐12. Journal of Cellular and Molecular Medicine, 23 (6). pp. 3974-3983. ISSN 1582-1838, ESSN: 1582-4934

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Official URL: https://onlinelibrary.wiley.com/doi/10.1111/jcmm.14283



Abstract

Failure of therapeutic approaches for the treatment of osteoarthritis (OA) based on the inhibition of metalloproteinases, might be because of their constitutive expres‐ sion in homeostasis, together with their network complexity. The knowledge of this network would contribute to selective target pathological conditions. In this sense, blockade of mediators produced by neighbouring joint cells, such as synovial fibro‐ blasts (SF), would prevent cartilage damage. Thus, we studied the contribution of ADAMTS‐7 and ‐12 from SF to cartilage oligomeric matrix protein (COMP) degrada‐ tion, and the signalling pathways involved in their expression. We report for the first time in SF, the involvement of ERK‐Runx2 axis and Wnt/β‐catenin signalling in ADAMTS‐12 and ADAMTS‐7 expressions, respectively, with the subsequent conse‐ quences in COMP degradation from cartilage extracellular matrix. After stimulation with IL‐1β or fibronectin fragments, we showed that ERK inhibition decreased Runx2 activation and ADAMTS‐12 expression in OA‐SF, also reducing Fn‐fs‐induced COMP degradation. Blockage of Wnt signalling by DKK1 reduced ADAMTS‐7 and COMP degradation in OA‐SF as well. In addition, Wnt7B expression was induced by IL‐1β and by itself, also increasing ADAMTS‐7. Our results could contribute to the develop‐ ment of disease‐modifying OA drugs targeting ADAMTS‐7 and ‐12 for the prevention of extracellular matrix components degradation like COMP.


Item Type:Article
Uncontrolled Keywords:ADAMTS‐12; ADAMTS‐7; COMP; Extracellular matrix; Osteoarthritis; Runx2 synovial fibroblasts; Wnt signalling fibroblasts, Wnt signalling
Subjects:Medical sciences > Medicine > Rheumatology
Medical sciences > Biology > Biochemistry
ID Code:56611
Deposited On:30 Jul 2019 08:43
Last Modified:30 Jul 2019 11:25

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