Facilitative role of circPVT1 in osteogenic differentiation potentials of bone marrow mesenchymal stem cells from patients with osteoporosis through the miR-30d-5p/ITGB3 axis

Abstract

ObjectiveThe critical role of circular RNAs (circRNAs) in osteoporosis (OP) has been highlighted. We tried to explore the role of circPVT1 in OP in relation to microRNA-30d-5p (miR-30d-5p) and ITGB3. MethodsAfter bone marrow collection, bone marrow mesenchymal stem cells (BMSCs) were isolated and identified. Then, Pearson coefficient was used to analyze the correlation among circPVT1, miR-30d-5p and ITGB3, and the binding sites were predicted and verified. Gain- and loss-of function assays in circPVT1, miR-30d-5p and ITGB3 were performed to analyze their effect on osteogenic differentiation of BMSCs. ResultsThe osteogenic differentiation of BMSCs from OP patients was significantly decreased, and reduced circPVT1 expression was found in the BMSCs from OP patients. Overexpression of circPVT1 stimulated the formation of calcified nodules, increased alkaline phosphatase activity, and enhanced the expression of osteogenic marker genes in the BMSCs from OP patients. Additionally, circPVT1 expression was negatively correlated with miR-30d-5p, and miR-30d-5p was negatively correlated with ITGB3 in OP patients. Mechanically, circPVT1 regulated the osteogenic differentiation potential of BMSCs by relieving the inhibition of miR-30d-5p on ITGB3 through the competitive endogenous RNA mechanism. ConclusionOur study highlighted a circPVT1/miR-30d-5p/ITGB3 axis in regulating osteogenic differentiation potential of BMSCs from OP patients.