Abstract: 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.
Keywords: CD8+ T cells; osteoarthritis; TIMP-1; VEGF; MMP-13
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Hsieh, J.-L.; Shiau, A.-L.; Lee, C.-H.; Yang, S.-J.; Lee, B.-O.; Jou, I.-M.; Wu, C.-L.; Chen, S.-H.; Shen, P.-C. CD8+ T Cell-Induced Expression of Tissue Inhibitor of Metalloproteinses-1 Exacerbated Osteoarthritis. Int. J. Mol. Sci. 2013, 14, 19951-19970.
Hsieh J-L, Shiau A-L, Lee C-H, Yang S-J, Lee B-O, Jou I-M, Wu C-L, Chen S-H, Shen P-C. CD8+ T Cell-Induced Expression of Tissue Inhibitor of Metalloproteinses-1 Exacerbated Osteoarthritis. International Journal of Molecular Sciences. 2013; 14(10):19951-19970.
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. 2013. "CD8+ T Cell-Induced Expression of Tissue Inhibitor of Metalloproteinses-1 Exacerbated Osteoarthritis." Int. J. Mol. Sci. 14, no. 10: 19951-19970.