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

International Journal of Molecular Sciences

Jeng-Long Hsieh²  Ai-Li Shiau¹  Che-Hsin Lee³  Shiu-Ju Yang⁴  Bih-O Lee⁷  I-Ming Jou⁵  Chao-Liang Wu⁶  Shun-Hua Chen¹ 

[1] Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; E-Mails:;Department of Nursing, Chung Hwa University of Medical Technology, Tainan 717, Taiwan; E-Mail:;Department of Microbiology, School of Medicine, China Medical University, Taichung 404, Taiwan; E-Mail:;Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; E-Mail:;Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; E-Mail:;Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; E-Mail:;Department of Nursing, Chang Gung University of Technology, Puzih, Chiayi County 613, Taiwan; E-Mail:

关键词: CD8⁺ T cells;    osteoarthritis;    TIMP-1;    VEGF;    MMP-13;   

DOI  :  10.3390/ijms141019951

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland