Zhong Xiaohuan, Wang Huixin, Jian Xinchun
Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Exp Ther Med. 2014 Jan;7(1):295-299. doi: 10.3892/etm.2013.1394. Epub 2013 Nov 8.
Insulin has been proposed to be a positive regulator of osteoblast proliferation and bone formation. mechanical loading is essential for maintaining skeletal integrity and bone mass. Since insulin and mechanical force activate similar signaling pathways in osteoblasts, it was hypothesized that insulin may affect mechanical stimulation in osteoblasts. The present study tested the hypothesis that insulin augments mechanical strain-induced signaling and early gene expression in MG63 cells via activation of the extracellular signal-regulated kinase (ERK) pathway and cyclooxygenase-2 (Cox-2) expression. Western blot analysis and quantitative polymerase chain reaction demonstrated respectively that insulin enhanced mechanical strain-induced ERK phosphorylation and Cox-2 expression levels in a dose-dependent manner. The effect of insulin on mechanical strain-induced Cox-2 expression was inhibited by blockade of the ERK pathway. In addition, echistatin, an inhibitor of integrin function, prevented the effects of insulin on mechanical strain-induced ERK phosphorylation and Cox-2 expression. The data obtained from this study suggested that insulin augments mechanical strain-induced Cox-2 expression levels via integrin-dependent activation of the ERK pathway in osteoblasts.
胰岛素被认为是成骨细胞增殖和骨形成的正向调节因子。机械负荷对于维持骨骼完整性和骨量至关重要。由于胰岛素和机械力在成骨细胞中激活相似的信号通路，因此推测胰岛素可能影响成骨细胞中的机械刺激。本研究检验了以下假设：胰岛素通过激活细胞外信号调节激酶（ERK）通路和环氧合酶-2（Cox-2）表达，增强MG63细胞中机械应变诱导的信号传导和早期基因表达。蛋白质免疫印迹分析和定量聚合酶链反应分别表明，胰岛素以剂量依赖的方式增强机械应变诱导的ERK磷酸化和Cox-2表达水平。ERK通路的阻断抑制了胰岛素对机械应变诱导的Cox-2表达的影响。此外，整合素功能抑制剂echistatin可阻止胰岛素对机械应变诱导的ERK磷酸化和Cox-2表达的影响。本研究获得的数据表明，胰岛素通过整合素依赖性激活成骨细胞中的ERK通路，增强机械应变诱导的Cox-2表达水平。
