{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:33:37Z","timestamp":1790706817867,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T00:00:00Z","timestamp":1381190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms141019951","type":"journal-article","created":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T11:43:08Z","timestamp":1381232588000},"page":"19951-19970","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["CD8+ T Cell-Induced Expression of Tissue Inhibitor of Metalloproteinses-1 Exacerbated Osteoarthritis"],"prefix":"10.3390","volume":"14","author":[{"given":"Jeng-Long","family":"Hsieh","sequence":"first","affiliation":[{"name":"Department of Nursing, Chung Hwa University of Medical Technology, Tainan 717, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2449-8547","authenticated-orcid":false,"given":"Ai-Li","family":"Shiau","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine,  National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che-Hsin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School  of Medicine, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiu-Ju","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Science, College of Medicine, National Cheng Kung University,  Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bih-O","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nursing, Chang Gung University of Technology, Puzih, Chiayi County 613, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Ming","family":"Jou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7821-9406","authenticated-orcid":false,"given":"Chao-Liang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Medicine,  National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine,  National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Chuan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Tainan Hospital, Department of Health, Executive Yuan, Tainan 700, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/00002281-200109000-00018","article-title":"Epidemiology of risk factors for osteoarthritis: Systemic factors","volume":"13","author":"Sowers","year":"2001","journal-title":"Curr. 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Res"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/10\/19951\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:49:42Z","timestamp":1760219382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/10\/19951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,8]]},"references-count":37,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2013,10]]}},"alternative-id":["ijms141019951"],"URL":"https:\/\/doi.org\/10.3390\/ijms141019951","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,8]]}}}