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CD8(+) T Cell-Induced Expression of Tissue Inhibitor of Metalloproteinses-1 Exacerbated Osteoarthritis

Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8(+) T cells in this disease. We investigated the effects of CD8(+) T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology. Using an...

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Detalles Bibliográficos
Autores principales: Hsieh, Jeng-Long, Shiau, Ai-Li, Lee, Che-Hsin, Yang, Shiu-Ju, Lee, Bih-O, Jou, I-Ming, Wu, Chao-Liang, Chen, Shun-Hua, Shen, Po-Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821596/
https://www.ncbi.nlm.nih.gov/pubmed/24108368
http://dx.doi.org/10.3390/ijms141019951
Descripción
Sumario:Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8(+) T cells in this disease. We investigated the effects of CD8(+) T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology. Using anterior cruciate ligament-transection (ACLT), OA was induced in mice. The knee joints were histologically assessed for manifestations of OA. The CD8(+) T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. Local expression of TIMP-1, matrix metalloproteinase (MMP)-13, and VEGF were examined. Cartilage degeneration was slower in CD8(+) T cell knockout mice than in control mice. CD8(+) T cells were activated once OA was initiated and expanded during OA progression. More CD8(+) T cells from splenocytes expressed TIMP-1 in ACLT-group mice than in Sham-group mice. The number of TIMP-1-expressing CD8(+) T cells in OA mice correlated with the disease severity. TIMP-1 expression in cartilage was co-localized with that of MMP-13 and VEGF. TIMP-1 protein was detected in synovium in which angiogenesis occurred. During the pathogenesis of OA, the expression of TIMP-1, VEGF and MMP-13 accompanying with CD8(+) T cells activation were increased. Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA.