Mechanism of mechanosensitive microRNA-337-3p regulation of bone mesenchymal stem cell proliferation and osteogenic differentiation-mediated spinal disuse osteoporosis
Mechanism of mechanosensitive microRNA-337-3p regulation of bone mesenchymal stem cell proliferation and osteogenic differentiation-mediated spinal disuse osteoporosis
Objective To investigate the mechanism of mechanosensitive microRNA-337-3p(miR-337-3p)regulation of bone mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation-mediated spinal disuse osteoporosis(DOP).Methods Mechanical traction stimulation was applied to BMSCs from humans,mice,and rats,and osteogenic differentiation was induced.Polymerase chain reaction(PCR)was used to detect the expression of miR-337-3p in BMSC of each group,and a gravity loss model was constructed by inhibiting the expression of miR-337-3p in rats.The bone mass of rats was examined by micro-computed tomography(Micro-CT)to evaluate the effect of miR-337-3p on the occurrence of DOP.The expression of miR-337-3p in rat BMSC was regulated,and the effect of miR-337-3p on the proliferation of rat BMSC detected by clone proliferation.The effect of miR-337-3p on osteogenic differentiation of rat BMSC was detected by alkaline phosphatase(ALP)staining,alizarin red staining and ectopic osteogenic differentiation.Target genes of miR-337-3p were identified by transcriptome sequencing and Western blotting.Results The expression of miR-337-3p from humans,mice,and rats BMSCs was inhibited by mechanical stretch stimulation,and induced a significant decrease in the expression of miR-337-3p in each group during the osteogenic differentiation process of BMSCs.Knockout and functional inhibition of miR-337-3p could alleviate bone loss caused by gravity loss,promote proliferation and osteogenic differentiation of rat BMSCs;overexpression of miR-337-3p could inhibit the proliferation and osteogenic differentiation of rat BMSCs.The expression of integrin β-like protein 1(ITGBL1)was inhibited by miR-337-3p.Conclusion miR-337-3p mediates spinal DOP by inhibiting the proliferation and differentiation of BMSCs,and inhibition of the expression and function of miR-337-3p can alleviate bone loss.