MicroRNA-140-5p was involved in osteonecrosis of the femoral head by inhibiting osteogenic diffentiation and migration of hBMSCs

Abstract

Background: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease and usually leads to disability. The unclear mechanism caused the trouble in diagnosis and early therapy of ONFH. Methods: We downloaded and analyzed the traumatic ONFH miRNA expression profile GSE89587. Then western blotting, PCR, alkaline phosphatase staining, wound healing assay and alizarin red S staining was used to investigate the effect of the selected miR-140-5p on human bone marrow-derived stem cells (hBMSCs). Furthermore, the relationship between miR-140-5p and BMP2 was detected by WB and we also used a siRNA of BMP2 to study whether silencing miR-140-5p could mitigate the damage caused by BMP2 interference.Results: 6 up-regulated miRNAs and 12 down-regulated miRNAs were identified and an upregulated miR-140-5p was selected for the downstream experiments. The further experiments showed that miR-140-5p upregulation in hBMSCs inhibited the expression of collagen type 1, OCN, and BMP2, reduced the ALP activity, mineralization, and migration ability of hBMSCs. In addition, inhibition of BMP2 inhibited osteogenesis of hBMSCs by regulating the BMP2-SMAD1/5/9-RUNX2 axis, while silencing miR-140-5p promoted osteogenesis of hBMSCs by regulating the BMP2-SMAD1/5/9-RUNX2 axis. Our study showed that miR-140-5p may be an emerging and valuable target for studying the mechanism of ONFH.