CircHGF suppressed cell proliferation and osteogenic differentiation of BMSCs in ONFH via inhibiting miR-25-3p binding to SMAD7

Xiaobo Feng; Qian Xiang; Jie Jia; Tingting Guo; Zhiwei Liao; Shuhua Yang; Xianyi Cai; Xianzhe Liu

doi:10.1016/j.omtn.2022.02.017

CircHGF suppressed cell proliferation and osteogenic differentiation of BMSCs in ONFH via inhibiting miR-25-3p binding to SMAD7

Mol Ther Nucleic Acids. 2022 Mar 1:28:99-113. doi: 10.1016/j.omtn.2022.02.017. eCollection 2022 Jun 14.

Authors

Xiaobo Feng¹, Qian Xiang², Jie Jia¹, Tingting Guo³, Zhiwei Liao¹, Shuhua Yang¹, Xianyi Cai¹, Xianzhe Liu¹

Affiliations

¹ Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
² Department of Orthopedics, Peking University Third Hospital, Beijing 100191, China.
³ Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Abstract

Steroid-induced osteonecrosis of the femoral head (ONFH) is a common and devastating bone disorder, which often results in progressive collapse of the femoral head and subsequent osteoarthritis. The proliferation ability and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) play critical roles in maintaining the structural and functional integrity of the femoral head to prevent ONFH. Until now, little has been known about the underlying mechanism of BMSCs differentiation disorder during ONFH progression. Circular RNAs (circRNAs) are considered to be vital non-coding RNAs functionally involved in various human diseases. However, whether and how circRNA regulates the proliferation and osteogenic differentiation of BMSCs in ONFH remain unclear. In this study, we analyzed the circRNA expression profile of five samples of BMSCs in ONFH and five samples of control by using circRNA microarray assays. We identified 182 differentially expressed circRNAs, among which 108 circRNAs were upregulated. We further investigated the effects of a significantly upregulated circRNA, circHGF, on the proliferation and osteogenic differentiation of BMSCs in vitro. Results showed that circHGF suppressed the proliferation and osteogenic differentiation of BMSCs in ONFH by targeting miR-25-3p/SMAD7 axis. Our findings provided a potential diagnostic and therapeutic strategy for ONFH.

Keywords: MT: Non-coding RNAs; SMAD7; bone marrow mesenchymal stem cells; circular RNA; osteogenic differentiation; osteonecrosis of the femoral head.