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Int. J. Mol. Sci. 2013, 14(10), 19951-19970; doi:10.3390/ijms141019951
Article

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

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1 Department of Nursing, Chung Hwa University of Medical Technology, Tainan 717, Taiwan 2 Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan 3 Department of Microbiology, School of Medicine, China Medical University, Taichung 404, Taiwan 4 Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan 5 Department of Nursing, Chang Gung University of Technology, Puzih, Chiayi County 613, Taiwan 6 Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan 7 Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan 8 Department of Orthopedic Surgery, Tainan Hospital, Department of Health, Executive Yuan, Tainan 700, Taiwan
* Author to whom correspondence should be addressed.
Received: 27 July 2013 / Revised: 11 September 2013 / Accepted: 22 September 2013 / Published: 8 October 2013
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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 CD8+ T cells; osteoarthritis; TIMP-1; VEGF; MMP-13
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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