RT Journal Article
T1 Healthy and Osteoarthritic Synovial Fibroblasts Produce a Disintegrin and Metalloproteinase with Thrombospondin Motifs 4, 5, 7, and 12
A1 Pérez García, Selene
A1 Gutiérrez Cañas, Irene
A1 Seoane Valiño, Iria V.
A1 Fernández, Julián
A1 Mellado, Mario
A1 Leceta Martínez, Javier
A1 Tío, Laura
A1 Villanueva Romero, Raúl
A1 Juarranz Moratilla, Yasmina
A1 Pérez Gomáriz, Rosa María
AB Current description of osteoarthritis includes the involvement of synovial inflammation. Studies contributing to understanding the mechanisms of cross-talk and feedback among the joint tissues could be relevant to the development of therapies that block disease progression. During osteoarthritis, synovial fibroblasts exposed to anomalous mechanical forces and an inflammatory microenvironment release factors such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) metalloproteinases that mediate tissue damage and perpetuate inflammation. We therefore studied the production of ADAMTS by synovial fibroblasts and their contribution to cartilage degradation. Moreover, we analyzed the implication of two mediators present in the osteoarthritis joint, IL-1β as proinflammatory cytokine, and 45-kDa fibronectin fragments as products of matrix degradation. We reported that synovial fibroblasts constitutively express and release ADAMTS 4, 5, 7, and 12. Despite the contribution of both mediators to the stimulation of Runx2 and Wnt/β-catenin signaling pathways, as well as to ADAMTS expression, promoting the degradation of aggrecan and cartilage oligomeric matrix protein from cartilage, fibronectin fragments rather than IL-1β played the major pathological role in osteoarthritis,contributing to the maintenance of the disease. Moreover, higher levels of ADAMTS 4 and 7 and a specific regulation of ADAMTS-12 were observed in osteoarthritis, suggesting them as new potential therapeutic targets. Therefore, synovial fibroblasts provide the biochemical tools to the chronicity and destruction of the osteoarthritic joints.
SN 0002-9440, ESSN: 1525-2191
YR 2016
FD 2016-09
LK https://hdl.handle.net/20.500.14352/17677
UL https://hdl.handle.net/20.500.14352/17677
LA eng
NO Instituto de Salud Carlos III
NO Comunidad de Madrid/FEDER
DS Docta Complutense
RD 1 jul 2025