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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.
摘要：
最近,microRNAs(miRs)在人类疾病中的作用已经得到证实。本研究旨在探讨microRNA-26a（miR-26a）在激素性股骨头坏死（SONFH）中的保护作用，并涉及zeste同源物2（EZH2）的增强子。收集SONFH患者和股骨颈骨折患者的股骨头(FH)样本,采用大肠杆菌内毒素结合大剂量类固醇脉冲法建立大鼠SONFH模型。血液流变学,血脂，炎症因子，通过一系列实验测量病理变化。此外，成骨细胞的检测，破骨细胞,miR-26a表达，EZH2表达，骨保护素（OPG）和骨保护素配体（OPGL），进行骨细胞凋亡。通过生物信息学和双荧光素酶报告基因分析，阐明了miR-26a与EZH2的靶关系。MiR-26a表达不佳，而EZH2在SONFH中高表达，miR-26a的升高可以抑制EZH2的表达。升高的miR-26a和降低的EZH2能够减缓骨细胞的凋亡，增加成骨细胞，减少破骨细胞，导致SONFH进程的抑制。此外,EZH2是miR-26a的靶基因。此外，EZH2的升高可以逆转miR-26a升高诱导的SONFH进程的抑制。我们发现miR-26a的上调和EZH2的敲低可以抑制SONFH的发展，这将有助于SONFH的治疗。
