Mechanical strain promotes osteoblastic differentiation through integrin-β1-mediated β-catenin signaling.

Abstract

As integrins are mechanoresponsive, there exists an intimate relationship between integrins and mechanical strain. Integrin-β1 mediates the impact of mechanical strain on bone. Mechanical strain induces bone formation through the activation of β-catenin pathways, which suggests that integrin-β1 mediates β-catenin signaling in osteoblasts in response to mechanical strain. In the present study, we examined the role of integrin-β1 in Wnt/β-catenin signal transduction in mechanically strained osteoblasts. MC3T3-E1 osteoblastic cells were transfected with integrin-β1 small interfering RNA(si-Itgβ1), and exposed to mechanical tensile strain of 2,500microstrain(µε) using a four-point bending device. The mechanical strain enhanced the mRNA expression of integrin-β1, the protein levels of phosphorylated (p-) glycogen synthase kinase-3β(GSK‑3β) and β-catenin, simultaneously increased the mRNA levels of runt-related transcriptional factor2(Runx2) and osteocalcin(OCN), the protein levels of bone morphogenetic protein(BMP)-2 and-4 and enhanced the alkaline phosphatase(ALP) activity of the ME3T3-E1 cells. The elevations were inhibited by si-Itgβ1. Additionally, the mechanical strain induced the nuclear translocation of β-catenin into the nucleus, which was also inhibited by si-Itgβ1. These findings indicated that mechanical strain promoted osteoblastic differentiation through integrin‑β1‑mediated β-catenin signaling.