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Healthy and Osteoarthritic Synovial Fibroblasts Produce a Disintegrin and Metalloproteinase with Thrombospondin Motifs 4, 5, 7, and 12

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Pérez García, Selene and Gutiérrez Cañas, Irene and Seoane Valiño, Iria V. and Fernández, Julián and Mellado, Mario and Leceta Martínez, Javier and Tío, Laura and Villanueva Romero, Raúl and Juarranz Moratilla, Yasmina and Pérez Gomáriz, Rosa María (2016) Healthy and Osteoarthritic Synovial Fibroblasts Produce a Disintegrin and Metalloproteinase with Thrombospondin Motifs 4, 5, 7, and 12. American Journal of Pathology, 186 (9). pp. 2449-2461. ISSN 0002-9440, ESSN: 1525-2191

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Official URL: http://ajp.amjpathol.org/article/S0002-9440(16)30212-7/fulltext



Abstract

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.


Item Type:Article
Uncontrolled Keywords:Osteoarthritis,Thrombospondin Motifs, IL-1β, Fibronectin, Cartilage Damage
Subjects:Medical sciences > Medicine > Biochemistry
Medical sciences > Medicine > Rheumatology
ID Code:41718
Deposited On:08 Mar 2017 11:17
Last Modified:01 Oct 2017 23:01

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