MiR-29b enhances the proliferation and migration of bone marrow mesenchymal stem cells in rats with castration-induced osteoporosis through the PI3K/AKT and TGF-β/Smad signaling pathways.

Abstract

The aim of the present study was to investigate the role of microRNA (miR)-29b in the proliferation and migration of bone marrow mesenchymal stem cells (BMSCs) in rats with castration-induced osteoporosis and the relevant mechanisms. The gene expression profiling microarray technique was utilized to sequence the BMSCs with overexpressed miR-29b. The intersection of the potential targets and the genes downregulated in the sequencing were utilized for GO enrichment analysis. Gene set enrichment analysis (GSEA) was employed to analyze the effect of miR-29b on signaling pathways. Additionally, the effects of miR-29b overexpression on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and transforming growth factor-β (TGF-β)/Drosophila mothers against decapentaplegic protein (Smad) signaling pathways were detected via RT-qPCR assay and western blotting. The expression level of miR-29b was found to be significantly reduced in bone marrow tissues of postmenopausal osteoporosis patients and BMSCs of rats with castration-induced osteoporosis established via ovariectomy. Based on transcriptome sequencing and bioinformatics software prediction, 76 potential targets of miR-29b were obtained, which were distinctly enriched in such biological processes as cell proliferation, cell cycle, cell migration and cell adhesion. The results of CCK-8 and EdU assays showed that overexpression of miR-29b overtly promoted the proliferation of BMSCs in rats with castration-induced osteoporosis. Moreover, the Transwell assay results revealed that the overexpression of miR-29b significantly facilitated the migration of BMSCs in rats with castration-induced osteoporosis. According to RT-qPCR assay and western blotting, miR-29b activated the PI3K/AKT and TGF-β/Smad signaling pathways. miR-29b exhibited a clearly lower expression level in the bone marrow tissues of the postmenopausal osteoporosis patients and BMSCs of rats with castration-induced osteoporosis established via ovariectomy. Overexpression of miR-29b was able to enhance the proliferation and migration ability of BMSCs in rats with castration-induced osteoporosis, and such an enhancement may be correlated with the activation of the PI3K/AKT and TGF-β/Smad signaling pathways.