骨芽細胞様細胞における持続的圧縮力によるheat shock protein25の発現誘導

It is well known that appropriate occlusal force promotes bone formation around implants, whereas bone atrophy and bone resorption develop under no mechanical stress or overstressing. It has been reported that shear stress loaded to osteoblasts induce increase of intracellular Ca^<2+> concentration, activation of protein kinase A, and upregulation of cyclooxygenase 2 (COX-2) gene, which lead to differentiation of osteoblasts. The purpose of this study was to clarify appropriate levels of stress for the bone remodeling and mechanotransduction signaling at molecular levels. We examined mRNA levels of genes associated with bone formation when compressing force was directly loaded to a mouse osteoblast-like cell line (MC3T3-E1) for 24 hours. Furthermore, we examined changes of gene expression under its stress by DNA microarray. COX-2, c-fos, and alkaline phosphatase (ALP) mRNAs were up-regulated in proportion to the stress value when compressing force was loaded. The analysis of cDNA macroarray showed that expression of bone morphogenetic protein 4 (BMP4) and BMP7, which promote differentiation of osteoblasts, was up-regulated. And the analysis of DNA microarray showed that compressing force upregulated expression of heat shock protein 25kDa (Hsp25). Induction of Hsp25 by compressing force to MC3T3-E1 cells was mediated mainly via integrin and ERK (Extracellular signal-regulated kinase) signaling pathways. Furthermore, it was revealed that extracellular Ca^<2+> influx from stretch activated calcium ion channel and L-type voltage-sensitive Ca^<2+> channel by compressing force was involved in induction of Hsp25 and COX-2. Because Hsp25 suppressed the activation of caspase 3, Hsp25 induced by compressing force seemed to act on anti-apoptosis. In conclusion, compressed force to MC3T3-E1 cells induced COX-2 and Hsp25, which lead to differentiation and suppression of apoptosis in osteoblasts.

公開日:2010年1月24日で登録したコンテンツは、国立情報学研究所において電子化したものです。