RT Journal Article
T1 Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast‐derived ADAMTS‐7 and ‐12
A1 Pérez García, Selene
A1 Carrión Caballo, Mar
A1 Villanueva Romero, Raúl
A1 Hermida Gómez, Tamara
A1 Fernández  Moreno, Mercedes
A1 Mellado, Mario
A1 Blanco, Francisco J.
A1 Juarranz Moratilla, Yasmina
A1 Gomáriz, Rosa P.
AB 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.
PB Wiley Open Acces
SN 1582-1838, ESSN: 1582-4934
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/13485
UL https://hdl.handle.net/20.500.14352/13485
LA eng
NO Instituto de Salud Carlos III/FEDER
NO RETICS
NO CIBER
DS Docta Complutense
RD 11 abr 2025