The protective effects of microRNA-26a in steroid-induced osteonecrosis of the femoral head by repressing EZH2

Abstract

Recently, the role of microRNAs (miRs) in human diseases has been verified. This study was determined to explore the protective effects of microRNA-26a (miR-26a) in steroid-induced osteonecrosis of the femoral head (SONFH) with the involvement of enhancer of zeste homologue 2 (EZH2). Femoral head (FH) samples from SONFH patients and patients with femoral neck fracture were collected, and rat SONFH models were established by Escherichia coli endotoxin combining with large dose steroid pulse assay. The hemorheology, blood lipid, inflammatory factors, and pathologic changes were measured by a series of experiments. Moreover, the detection of osteoblasts, osteoclasts, miR-26a expression, EZH2 expression, osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL), and the apoptosis of osteocytes were conducted. The target relation between miR-26a and EZH2 was clarified by bioinformatics and dual-luciferase reporter gene assay. MiR-26a was poorly expressed, while EZH2 was highly expressed in SONFH, and the elevation of miR-26a could repress EZH2 expression. Elevated miR-26a and reduced EZH2 were able to decelerate the apoptosis of osteocytes, increase osteoblasts, and decrease osteoclasts, resulting in a repression of SONFH progression. Additionally, EZH2 was a target gene of miR-26a. Furthermore, the elevation of EZH2 could reverse the repression of SONFH progression that is induced by elevated miR-26a. We found that up-regulation of miR-26a and knockdown of EZH2 could suppress the development of SONFH, which would contribute to the therapy of SONFH.