Li Gang, Liu Haifeng, Zhang Xiaogang, Liu Xingchao, Zhang Guodong, Liu Qinghe
Department of Orthopedics, Hebei Yanda Hospital, Hebei Medical University, Sanhe, China.
Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Cell Cycle. 2020 Mar;19(5):551-566. doi: 10.1080/15384101.2020.1717043. Epub 2020 Feb 13.
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.
最近，微小RNA（miR）在人类疾病中的作用已得到证实。本研究旨在探讨微小RNA-26a（miR-26a）在涉及zeste同源物2增强子（EZH2）的类固醇诱导的股骨头坏死（SONFH）中的保护作用。收集了SONFH患者和股骨颈骨折患者的股骨头（FH）样本，并通过大肠杆菌内毒素结合大剂量类固醇脉冲试验建立大鼠SONFH模型。通过一系列实验测量血液流变学、血脂、炎症因子和病理变化。此外，还进行了成骨细胞、破骨细胞、miR-26a表达、EZH2表达、骨保护素（OPG）和骨保护素配体（OPGL）的检测以及骨细胞凋亡的检测。通过生物信息学和双荧光素酶报告基因试验阐明了miR-26a与EZH2之间的靶向关系。miR-26a在SONFH中表达较低，而EZH2表达较高，miR-26a的升高可抑制EZH2表达。升高的miR-26a和降低的EZH2能够减缓骨细胞凋亡，增加成骨细胞，减少破骨细胞，从而抑制SONFH的进展。此外，EZH2是miR-26a的靶基因。此外，EZH2的升高可逆转miR-26a升高所诱导的SONFH进展的抑制作用。我们发现上调miR-26a和敲低EZH2可抑制SONFH的发展，这将有助于SONFH的治疗。
