ERK5信号通路介导流体剪切力对MC3T3-E1成骨细胞MMPs、TIMPs表达的影响
ERK5 signaling pathway mediates the effects of fluid shear stress on the expression of MMPs and TIMPs in MC3T3-E1 osteoblasts
  
DOI:10.3969/j.issn.1006.7108.2018.05.006
中文关键词:  流体剪切力  MC3T3-E1 细胞  细胞外信号调节激酶5  基质金属蛋白酶  基质金属蛋白酶抑制剂
英文关键词:Fluid shear stress  MC3T3- E1 cell  Extracellular signal-regulated kinase 5  Matrix metalloproteinase  Matrix metalloproteinase inhibitory factor
基金项目:国家自然科学基金(81672207);甘肃省青年科技研究基金项目(1506RJYA233)
作者单位
杨全增1,2 张成俊1,2 丁宁 1,2 李忠浩1,2 夏亚一1,2* 1. 兰州大学第二医院甘肃 兰州 730000 2. 甘肃省骨关节疾病研究重点实验室甘肃 兰州 730000 
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中文摘要:
      目的 观察流体剪切力(fluid shear stress,FSS)作用下,MC3T3-E1 成骨细胞中细胞基质金属蛋白酶(matrix metalloproteinases,MMPs)和基质金属蛋白酶抑制剂(tissue inhibitors of metalloproteinases,TIMPs)的表达情况,并探讨 ERK5 信号通路在其中的作用。方法 对MC3T3-E1成骨细胞进行不同的处理,分为正常组、XMD8-92组 、FSS组和FSS+XMD8-92 组,对FSS组施加 12 dyn /cm2 流体剪切力,采用蛋白免疫印迹法分别检测P-ERK5、ERK5、 MMPs和TIMPs 蛋白水平的变化。结果 生理强度(12 dyn/cm 2 )的流体剪切力作用于MC3T3-E1成骨细胞45min后能显著上调MMPs的表达,下调TIMPs的表达,但此效应可被 ERK5 高选择性抑制剂 XMD8-92 阻断。结论 ERK5 信号通路调控流体剪切力对成骨细胞MMPs、TIMPs蛋白的表达。
英文摘要:
      Objective To observe the expression matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in MC3T3-E1 osteoblastic cells induced by fluid shear stress, as well as to study the effect of ERK5 signaling pathway in it. Methods MC3T3-E1 cells were treated with FSS or XMD8-92 alone, or in combination, and were subjected to fluid shear stress (12dyn /cm2) for 0, 15, 30, 45, 60 minutes. The protein levels of extracellular signal-regulated kinase 5 (ERK5), phospho-ERK5 (P-ERK5), MMPS and TIMPs were detected by Western blotting. Results For MC3T3-E1 cells cultured in vitro, loading of 12 dyn /cm2 fluid shear stress for 45 minutes could up regulate the expression of MMPs, down regulate the expression of TIMPs, but the effect was blocked by XMD8-92 (a highly selective inhibitor of ERK5 activity). Conclusions ERK5 signaling pathway plays essential roles in the expression of MMPs and TIMPs induced by fluid shear stress in the MC3T3-E1 osteoblastic cells.
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