p38 signaling in titanium particle-induced MMP-2 secretion and activation in differentiating MC3T3-E1 cells
p38 signaling in titanium particle-induced MMP-2 secretion and activation in differentiating MC3T3-E1 cells
复制标题
钛颗粒诱导分化 MC3T3-E1 细胞 MMP-2 分泌和激活中的 p38 信号传导
DOI：
10.1002/jbm.a.34956
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发表时间：
2014-08-01
影响因子：
4.9
通讯作者：
Xu, Wei
中科院分区：
文献类型：
--
作者：
Chen, Ming;Chen, Pei-Min;Xu, Wei
磨损颗粒引起的假体周围骨溶解是关节置换术后无菌性松动的重要原因。骨质溶解的分子机制仍有待描述。在这项研究中，培养的MC 3 T3-E1细胞与钛颗粒一起孵育。我们研究了p38丝裂原活化蛋白激酶在MMP-2表达中的作用。我们的结果表明，暴露于钛颗粒的MC 3 T3-E1细胞的MMP-2和MT 1-MMP mRNA水平显著增加，而TIMP-2 mRNA水平无变化。在MC 3 T3-E1细胞中，MMP-2，MT 1-MMP和活性p38的蛋白表达在钛颗粒暴露后也升高，如通过Western blot和Biotrak活性分析检测到的。抑制研究表明，特异性p38抑制剂SB 203580完全消除了钛颗粒诱导的MMP-2和MT 1-MMP产生的增加。此外，我们的研究结果表明，条件mediastimulated破骨细胞的形成与MMP-2活性的成骨细胞的挑战与钛颗粒。这项研究表明，p38信号是所需的MMP-2活性在成骨细胞在磨损颗粒诱导的条件下。MMP-2可能作为分解代谢因子或促炎因子，导致假体周围骨溶解。因此，p38通路和MMP-2可能在无菌性松动的发生中起关键作用。(C)2013 Wiley Periodicals，Inc.
The periprosthetic osteolysis induced by wear particles contributes to aseptic loosening after joint arthroplasty. The molecular mechanism underlying osteolysis remains to be described. In this study, cultured MC3T3-E1 cells were incubated with titanium particles. We investigated the role of p38 mitogen-activated protein kinase in the expression of MMP-2 in response to wear particles. Our results demonstrated MC3T3-E1 cells exposed to titanium particles had significantly increased levels of MMP-2 and MT1-MMP mRNA, whereas the TIMP-2 mRNA level was unchanged. In MC3T3-E1 cells, the protein expression of MMP-2, MT1-MMP, and active p38 was also elevated after titanium particle exposure, as detected by Western blot and Biotrak activity analyses. Inhibition studies showed that the specific p38 inhibitor SB203580 completely abrogated the increase in MMP-2 and MT1-MMP production induced by the titanium particles. Moreover, our results revealed that conditioned mediastimulated osteoclast formation was related to the MMP-2 activity of osteoblasts that were challenged with Ti particles. This study demonstrated that p38 signaling is required for MMP-2 activity in osteoblasts under wear particle-induced conditions. MMP-2 could act as a catabolic element or a proinflammatory factor contributing to periprosthetic osteolysis. Therefore, the p38 pathway and MMP-2 may play a critical role in the development of aseptic loosening. (C) 2013 Wiley Periodicals, Inc.