震荡流体剪切力通过ERK5信号通路促进成骨细胞增殖
Oscillatory shear stress promotes MC3T3-E1 cells proliferation via ERK5 signaling pathway
  
DOI:10.3969/j.issn.1006-7108.2016.10.003
中文关键词:  震荡流体剪切力  Extracellular signal-regulated kinase 5  成骨细胞  增殖
英文关键词:Oscillatory shear stress  Extracellular signal-regulated kinase 5  Osteoblast  Proliferation
基金项目:国家自然科学基金(81560361);甘肃省自然科学基金(1506RJZA240);兰州大学第二医院院内博士科研基金(ynbskyjj2015-2-9)
作者单位
张波1,2 杨利娟3 丁宁1,2 许田恩1,2 郭来威1,2 孟会强1,2 汪静2 王翠芳2 安丽萍2 马靖琳2夏亚一1* 1. 兰州大学第二医院骨科,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 3. 焦作市第二人民医院妇瘤科,河南 焦作 454150 
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中文摘要:
      目的 探讨震荡流体剪切力(oscillatory shear stress, OSS)通过ERK5信号通路在诱导成骨细胞增殖中发挥的作用。 方法 对成骨MC3T3-E1细胞进行不同的处理,分为正常组、OSS组、XMD8-92组和OSS+XMD8-92组。采用MTT实验分别测定4组细胞的增殖活性并绘制生长曲线;蛋白免疫印迹法分别检测P-ERK5、ERK5和Cyclin D1等蛋白水平变化。结果 OSS可显著增加成骨MC3T3-E1细胞增殖活性,但此效应可被ERK5高选择性抑制剂XMD8-92阻断。OSS可显著上调Cyclin D1的表达,而XMD8-92可显著下调OSS诱导的Cyclin D1的表达。 结论 OSS通过激活ERK5信号通路促进成骨细胞增殖,Cyclin D1是ERK5信号通路下游的重要靶点基因。
英文摘要:
      Objective The effect of ERK5 pathway on oscillatory shear stress (OSS) increased MC3T3-E1 cells proliferation was explored. Methods MC3T3-E1 cells were treated with OSS, XMD8-92 alone, or in combination. The proliferation absorbance of osteoblasts was detected using MTT assay, the protein levels of Extracellular signal-regulated kinase 5 (ERK5), P-ERK5, and Cyclin D1 were evaluated with western blot analysis. Results OSS (0.6±12 dyn/cm2) for 1h significantly enhanced osteoblasts proliferation, but the cellular proliferation was blocked by XMD8-92 (a highly selective inhibitor of ERK5 activity), suggesting that ERK5 is involved in OSS-induced osteoblasts proliferation. The protein levels of Cyclin D1 under OSS were elevated, but XMD8-92 markedly suppressed Cyclin D1 expression with exposure to OSS. Conclusions OSS promotes osteoblasts proliferation via ERK5 pathway, and Cyclin D1 is the crucial downstream target of ERK5 pathway.
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