Yingjie Liu1, Yang Zong1, Haojie Shan1, Yiwei Lin1, Wenyang Xia1, Nan Wang2, Lihui Zhou3, Youshui Gao1, Xin Ma4, Chaolai Jiang5. 1. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. 2. Department of Emergency, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. 3. Department of Orthopaedic Surgery, Xiangshan First People's Hospital, Ningbo 315700, Zhejiang, China. 4. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: drmx330@126.com. 5. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: bakehim@alumni.sjtu.edu.cn.
Abstract
BACKGROUND: Clinical treatment with high-dose of steroid hormone causes steroid-induced osteonecrosis of the femoral head (SONFH), whereas the internal regulation mechanism remains elusive. Numerous studies have reported that microRNAs participated in the development of SONFH through modulating gene expression. The aim of the current study was to clarify the function of microRNA-23b-3p (miR-23b-3p) and ZNF667 in SONFH. EXPERIMENTAL DESIGN: Bioinformatics prediction and luciferase reporter system were utilized to confirm the target relation between miR-23b-3p and ZNF667. To examine the function of miR-23b-3p in vivo, rat SONFH models were established by specific inducers. The morphological changes, plasma viscosity, blood lipid, and inflammatory cytokines were measure by corresponding experiments. RESULTS: MiR-23b-3p and ZNF667 was negatively correlated in SONFH patient tissues, miR-23b-3p was down-regulated, while ZNF667 was up-regulated. MiR-23b-3p targeted ZNF667, the expression level of ZNF667 was suppressed by miR-23b-3p activation whereas strengthened by miR-23b-3p inhibition. SONHF rats with overexpressed miR-23b-3p displayed alleviated symptoms, including reduced plasma viscosity, declined blood lipids, decreased levels of pro-inflammatory cytokines and improved bone integrality. Moreover, elevation of ZNF667 reversed the repression of SONFH induced by miR-23b-3p overexpression. CONCLUSIONS: We found that miR-23b-3p played a protective role in SONFH by targeting ZNF667, which provided a novel reference for SONFH prevention and therapy.
BACKGROUND: Clinical treatment with high-dose of steroid hormone causes steroid-induced osteonecrosis of the femoral head (SONFH), whereas the internal regulation mechanism remains elusive. Numerous studies have reported that microRNAs participated in the development of SONFH through modulating gene expression. The aim of the current study was to clarify the function of microRNA-23b-3p (miR-23b-3p) and ZNF667 in SONFH. EXPERIMENTAL DESIGN: Bioinformatics prediction and luciferase reporter system were utilized to confirm the target relation between miR-23b-3p and ZNF667. To examine the function of miR-23b-3p in vivo, ratSONFH models were established by specific inducers. The morphological changes, plasma viscosity, blood lipid, and inflammatory cytokines were measure by corresponding experiments. RESULTS:MiR-23b-3p and ZNF667 was negatively correlated in SONFHpatient tissues, miR-23b-3p was down-regulated, while ZNF667 was up-regulated. MiR-23b-3p targeted ZNF667, the expression level of ZNF667 was suppressed by miR-23b-3p activation whereas strengthened by miR-23b-3p inhibition. SONHF rats with overexpressed miR-23b-3p displayed alleviated symptoms, including reduced plasma viscosity, declined blood lipids, decreased levels of pro-inflammatory cytokines and improved bone integrality. Moreover, elevation of ZNF667 reversed the repression of SONFH induced by miR-23b-3p overexpression. CONCLUSIONS: We found that miR-23b-3p played a protective role in SONFH by targeting ZNF667, which provided a novel reference for SONFH prevention and therapy.