miR-4739/ITGA10/PI3K signaling regulates differentiation and apoptosis of osteoblast.

Introduction: To probe the impacts and biological roles of miR-4739/ITGA10 on the proliferation, differentiation and apoptosis of osteoblasts. Methods: Bioinformatics analysis was conducted to screen the key genes in osteoporosis. The upstream miRNAs of ITGA10 were predicted by TargetScan. KEGG pathway enrichment analysis was performed by DAVID database. The osteoblast proliferation and apoptosis were measured using CCK-8 and flow cytometry. The differentiation markers were measured by qRT-PCR and western blotting. The luciferase reporter assay was conducted to verify the binding of miR-4739 to ITGA10. Results: ITGA10 was down-regulated in patients with osteoporosis and identified as the key gene in osteoporosis by the bioinformatics analysis. Then the prediction provided by TargetScan indicated that miR-4739 was the potential upstream miRNA for ITGA10. And the following luciferase reporter assay showed that miR-4739 could bind to ITGA10 3'UTR. Furthermore, the miR-4739 inhibitor promoted osteoblasts proliferation, differentiation, and inhibited cell apoptosis by increasing the expression of ITGA10 and subsequently activating the PI3K/AKT signaling pathway. Conclusions: Overall, we proved that the higher expression of miR-4739 participated in the progression of osteoporosis by targeting ITGA10 and modulating PI3K/AKT signaling pathway, and perhaps miR-4739/ITGA10 axis could be potential diagnostic markers and therapeutic target for osteoporosis.