title: Insulin augments mechanical strain-induced ERK activation and cyclooxygenase-2 expression in MG63 cells through integrins.
abstract: Insulin has been proposed to be a positive regulator of osteoblast proliferation and bone formation.In vivomechanical 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.
authors.affiliation: Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Jian
keywords: cyclooxygenase-2; extracellular signal-regulated kinase; insulin; mechanical strain; osteoblast