Department of Orthopedics, The Second Hospital of Jilin University, Ziqiang Street 218, Changchun, Jilin 130041, China; Research Centre of the Second Hospital of Jilin University, Ziqiang Street 218, Changchun, Jilin 130041, China; The Engineering Research Centre of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province, Ziqiang Street 218, Changchun, Jilin 130041, China.
Department of Orthopedics, The Second Hospital of Jilin University, Ziqiang Street 218, Changchun, Jilin 130041, China; Research Centre of the Second Hospital of Jilin University, Ziqiang Street 218, Changchun, Jilin 130041, China; The Engineering Research Centre of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province, Ziqiang Street 218, Changchun, Jilin 130041, China.
Bone. 2020 Apr;133:115258. doi: 10.1016/j.bone.2020.115258. Epub 2020 Feb 1.
Steroid-induced osteonecrosis of the femoral head (SONFH) is a common debilitating orthopedic disease. The bone marrow mesenchymal stem cells (BMSCs) are a type of mesenchymal stem cells which play crucial roles in bone repair. The adipogenic/osteogenic differentiation disorder of BMSCs has been widely perceived contributing to SONFH. However, the regulatory mechanism of BMSCs differentiation disorder still remains unclear. Circular RNA (circRNA), a kind of stable ncRNA, plays important roles in regulating gene expression via various ways. To date, there are no studies to uncover the circRNA expression profile and screen out the key circRNAs playing crucial roles in adipogenic/osteogenic differentiation disorder of SONFH-BMSCs. In present study, we detected the circRNA expression profiles in SONFH-BMSCs for the first time. A total of 820 circRNAs were differentially expressed in SONFH-BMSCs, including 460 up- and 360 down-regulated circRNAs. Bioinformatics analysis indicates circRNA CDR1as, one up-regulated circRNA, may play crucial role in adipogenic/osteogenic differentiation disorder of SONFH-BMSCs via CDR1as-miR-7-5p-WNT5B axis. Knocking-down CDR1as resulted in increasing of osteogenic differentiation and decreasing of adipogenic differentiation of BMSCs, while over-expressing CDR1as resulted in decreasing of osteogenic differentiation and increasing of adipogenic differentiation of BMSCs. The miR-7-5p binding sites of CDR1as and WNT5B were verified by luciferase reporter gene assay. Our study may provide new insights into the molecular mechanisms of osteogenic/adipogenic differentiation disorder of SONFH-BMSCs and new biomarkers for the diagnosis and treatment of SONFH.
激素诱导性股骨头坏死（SONFH）是一种常见的使人虚弱的骨科疾病。骨髓间充质干细胞（BMSCs）是一种间充质干细胞，在骨修复中起着至关重要的作用。BMSCs 的成脂/成骨分化障碍已被广泛认为是导致 SONFH 的原因。然而，BMSCs 分化障碍的调节机制仍不清楚。环状 RNA（circRNA）是一种稳定的 ncRNA，通过多种方式在调节基因表达中发挥重要作用。迄今为止，尚无研究揭示 SONFH-BMSCs 中成脂/成骨分化障碍的 circRNA 表达谱，并筛选出发挥关键作用的关键 circRNAs。在本研究中，我们首次检测了 SONFH-BMSCs 中的 circRNA 表达谱。在 SONFH-BMSCs 中，共有 820 个 circRNA 表达差异，包括 460 个上调和 360 个下调 circRNA。生物信息学分析表明，上调的 circRNA CDR1as 可能通过 CDR1as-miR-7-5p-WNT5B 轴在 SONFH-BMSCs 的成脂/成骨分化障碍中发挥关键作用。敲低 CDR1as 导致 BMSCs 的成骨分化增加和脂肪分化减少，而过表达 CDR1as 导致 BMSCs 的成骨分化减少和脂肪分化增加。CDR1as 和 WNT5B 的 miR-7-5p 结合位点通过荧光素酶报告基因检测得到验证。我们的研究可能为 SONFH-BMSCs 成骨/成脂分化障碍的分子机制提供新的见解，并为 SONFH 的诊断和治疗提供新的生物标志物。
