重组组织金属蛋白酶抑制剂-3蛋白诱导小鼠成骨细胞MC3T3-E1凋亡。
Recombinant tissue metalloproteinase inhibitor-3 protein induces apoptosis of murine osteoblast MC3T3-E1.
作者信息
Yuan L-Q, Liu Y-S, Luo X-H, Guo L-J, Xie H, Lu Y, Wu X-P, Liao E-Y
机构信息
Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
出版信息
Amino Acids. 2008 Jun;35(1):123-7. doi: 10.1007/s00726-007-0614-0. Epub 2007 Dec 21.
Tissue inhibitor of metalloproteinases (TIMPs) plays an essential role in the regulation of bone metabolism. Here we report that recombinant tissue metalloproteinase inhibitor-3 (TIMP-3) protein induces the apoptosis of MC3T3-E1 osteoblasts. Cell apoptosis was detected by sandwich-enzyme-immunoassay. Fas and Fasl protein levels were determined by Western blot analysis. The enzyme substrate was used to assess the activation of caspase-3 and caspase-8. The phosphorylation of JNK, p38 and ERK1/2 was examined by Western blot analysis. The ELISA suggested that TIMP-3 promoted MC3T3-E1 cell apoptosis. TIMP-3 treatment induced the expression of Fas and Fasl proteins, and the activation of caspase-8 and caspase-3. TIMP-3 treatment induced p38 and ERK phosphorylation. SB203580 and PD98059, the inhibitor of p38 and ERK, respectively, abolished the TIMP-3 effect on osteoblast apoptosis. In conclusion, the signal pathway through which TIMP-3 induces MC3T3-E1 cell apoptosis, mediated by Fas and involves the p38 and ERK signal transduction pathways.
金属蛋白酶组织抑制剂（TIMPs）在骨代谢调节中起重要作用。在此我们报告，重组组织金属蛋白酶抑制剂-3（TIMP-3）蛋白可诱导MC3T3-E1成骨细胞凋亡。通过夹心酶免疫测定法检测细胞凋亡。通过蛋白质印迹分析确定Fas和Fasl蛋白水平。使用酶底物评估caspase-3和caspase-8的活化。通过蛋白质印迹分析检测JNK、p38和ERK1/2的磷酸化。酶联免疫吸附测定表明TIMP-3促进MC3T3-E1细胞凋亡。TIMP-3处理诱导Fas和Fasl蛋白表达以及caspase-8和caspase-3的活化。TIMP-3处理诱导p38和ERK磷酸化。p38和ERK的抑制剂SB203580和PD98059分别消除了TIMP-3对成骨细胞凋亡的影响。总之，TIMP-3诱导MC3T3-E1细胞凋亡的信号通路由Fas介导，涉及p38和ERK信号转导通路。
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