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Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast‐derived ADAMTS‐7 and ‐12 Pérez García, Selene Carrión Caballo, Mar Villanueva Romero, Raúl Hermida Gómez, Tamara Fernández Moreno, Mercedes Mellado, Mario Blanco, Francisco J. Juarranz Moratilla, Yasmina Gomáriz, Rosa P. 577.112.6 616.72-002 ADAMTS‐12 ADAMTS‐7 COMP Extracellular matrix Osteoarthritis Runx2 synovial fibroblasts Wnt signalling fibroblasts Wnt signalling Reumatología Bioquímica (Biología) 3205.09 Reumatología 2302 Bioquímica 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. Instituto de Salud Carlos III/FEDER RETICS CIBER Depto. de Biología Celular Fac. de Ciencias Biológicas TRUE pub 2023-06-17T13:26:24Z 2023-06-17T13:26:24Z 2019 journal article https://hdl.handle.net/20.500.14352/13485 1582-1838, ESSN: 1582-4934 10.1111/jcmm.14283 eng (RD16/0012/0002 RD16/0012/0006 and RD16/0012/0008) SAF 2017‐82940‐R PI17/00027 and PI16/2124 (CB06/01/0040) Atribución 3.0 España https://creativecommons.org/licenses/by/3.0/es/ open access application/pdf Wiley Open Acces