CD8+ T cell-induced expression of tissue inhibitor of metalloproteinses-1 exacerbated osteoarthritis.
CD8+ T cell-induced expression of tissue inhibitor of metalloproteinses-1 exacerbated osteoarthritis.
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DOI：
10.3390/ijms141019951
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发表时间：
2013-10-08
影响因子：
5.6
通讯作者：
Shen PC
中科院分区：
文献类型：
--
作者：
Hsieh JL;Shiau AL;Lee CH;Yang SJ;Lee BO;Jou IM;Wu CL;Chen SH;Shen PC
尽管T细胞参与了骨关节炎（OA）的发病机制，但关于CD 8 + T细胞在这种疾病中的作用知之甚少。我们研究了CD 8 + T细胞和金属蛋白酶组织抑制剂1（TIMP-1）的表达对关节病理学的影响。使用前交叉韧带横断（ACLT），在小鼠中诱导OA。对膝关节进行组织学评估，以了解OA的表现。分别用流式细胞术和免疫化学方法对脾细胞和滑膜中的CD 8 + T细胞进行评价。检测TIMP-1、基质金属蛋白酶（MMP）-13和VEGF的局部表达。CD 8 + T细胞敲除小鼠的软骨退化比对照小鼠慢。一旦OA开始，CD 8 + T细胞被激活，并在OA进展期间扩增。ACLT组小鼠脾CD 8 + T细胞表达TIMP-1的比例高于Sham组。OA小鼠中表达TIMP-1的CD 8 + T细胞的数量与疾病的严重程度相关。软骨组织中TIMP-1与MMP-13、VEGF的表达呈共定位关系。TIMP-1蛋白在滑膜组织中表达，且在滑膜组织中有血管生成。在OA发病过程中，TIMP-1、VEGF和MMP-13的表达增加，同时伴有CD 8 + T细胞的活化。抑制TIMP-1的表达可延缓OA的进展。
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.
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影响因子：
4
作者：
Nakamura, Hiroshi;Tanaka, Michiaki;Nishioka, Kusuki
通讯作者：
Nishioka, Kusuki
影响因子：
1.8
作者：
Muir, Peter;Kelly, Jennifer L.;Plisch, Erin
通讯作者：
Plisch, Erin
骨关节炎的炎症。
影响因子：
5.1
作者：
Goldring MB;Otero M
通讯作者：
Otero M
影响因子：
11.4
作者：
Jung, Ki-Kyung;Liu, Xu-Wen;Kim, Hyeong-Reh Choi
通讯作者：
Kim, Hyeong-Reh Choi
影响因子：
4.4
作者：
Leonardi, A;Cortivo, R;Abatangelo, G
通讯作者：
Abatangelo, G