Mechanical strain promotes osteogenic differentiation of bone mesenchymal stem cells from ovariectomized rats via the phosphoinositide 3-kinase/Akt signaling pathway

摘要

Osteoporosis has become an overwhelming public health problem worldwide. As an elementary physiological factor to regulate bone formation and regeneration, mechanical strain may be used as a non-invasive intervention in osteoporosis prevention and treatment. However, little is known regarding the underlying mechanism. The aim of the current study was to investigate the effect of continuous mechanical strain (CMS) on osteogenic differentiation of bone mesenchymal stem cells (BMSCs) from ovariectomized rats (OVX BMSCs). In addition, involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in biomechanical signal transduction and its function were evaluated. The results demonstrated that OVX BMSCs subjected to CMS exhibited higher alkaline phosphatase (ALP) activity and deeper staining at 24 and 48 h. In addition, CMS upregulated the mRNA expression levels of ALP, collagen type I, runt related transcription factor 2 (Runx2), as well as the protein expression level of Runx2 in a time-dependent manner. The PI3K/Akt signaling pathway was rapidly activated by CMS, with its phosphorylation level reaching its maximum in a short duration and a large quantity of phosphorylated-Akt remaining in the nucleus. Pre-treatment with a selective blocker significantly blocked the strain-induced activation of PI3K/Akt and reduced the commitment of OVX BMSCs into osteoblasts, demonstrating a dominated regulative effect of PI3K/Akt signaling in strain-induced osteogenesis. These results indicated that CMS induced the early differentiation of OVX BMSCs towards an osteogenic phenotype by activating the PI3K/Akt signaling pathway.