Feng Xiaobo, Xiang Qian, Jia Jie, Guo Tingting, Liao Zhiwei, Yang Shuhua, Cai Xianyi, Liu Xianzhe
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Orthopedics, Peking University Third Hospital, Beijing 100191, China.
Mol Ther Nucleic Acids. 2022 Mar 1;28:99-113. doi: 10.1016/j.omtn.2022.02.017. eCollection 2022 Jun 14.
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 . 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.
类固醇诱导的股骨头坏死（ONFH）是一种常见且具有破坏性的骨疾病，常导致股骨头进行性塌陷及随后的骨关节炎。骨髓间充质干细胞（BMSCs）的增殖能力和成骨分化在维持股骨头的结构和功能完整性以预防ONFH中起着关键作用。到目前为止，关于ONFH进展过程中BMSCs分化紊乱的潜在机制知之甚少。环状RNA（circRNAs）被认为是在各种人类疾病中发挥功能作用的重要非编码RNA。然而，circRNA是否以及如何调节ONFH中BMSCs的增殖和成骨分化仍不清楚。在本研究中，我们通过使用circRNA微阵列分析，分析了ONFH中五个BMSCs样本和五个对照样本的circRNA表达谱。我们鉴定出182个差异表达的circRNAs，其中108个circRNAs上调。我们进一步研究了一个显著上调的circRNA，即circHGF，对BMSCs增殖和成骨分化的影响。结果表明，circHGF通过靶向miR-25-3p/SMAD7轴抑制ONFH中BMSCs的增殖和成骨分化。我们的研究结果为ONFH提供了一种潜在的诊断和治疗策略。
