Department of orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, Jiangsu Province, China.
Department of orthopedics, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu Province, China.
Int J Biol Macromol. 2024 Nov;281(Pt 1):136175. doi: 10.1016/j.ijbiomac.2024.136175. Epub 2024 Sep 30.
Osteoarthritis (OA) is the most common joint disease with high prevalence and incidence. Increasing reports has indicated that circular RNAs (circRNAs) are implicated in OA progression. Nevertheless, the roles and functions of most circRNAs in OA remain to be elucidated. In this study, we emphatically discussed circ-IQGAP1 (circ_0104873) in OA. Firstly, we discovered that circ_0104873 was dramatically overexpressed during osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Several functional assays demonstrated that circ_0104873 inhibition repressed BMSCs proliferation and osteogenic differentiation. Moreover, mechanism assays also revealed that circ_0104873 sponged microRNA-875-5p (miR-875-5p) to up-regulate notch receptor 3 (NOTCH3), thereby activating the Notch signaling pathway. Rescue assays disclosed that circ_0104873 contributed to the development of OA via targeting miR-875-5p/NOTCH3 axis. In conclusion, circ_0104873 promoted the progression of OA by miR-875-5p/NOTCH3/Notch signaling pathway, which might provide a promising target for OA treatment.
骨关节炎（OA）是一种最常见的关节疾病，具有较高的发病率和患病率。越来越多的报道表明，环状 RNA（circRNAs）参与 OA 的进展。然而，大多数 circRNAs 在 OA 中的作用和功能仍有待阐明。在本研究中，我们重点讨论了 OA 中的 circ-IQGAP1（circ_0104873）。首先，我们发现 circ_0104873 在骨髓间充质干细胞（BMSCs）成骨分化过程中显著过表达。几项功能测定表明，circ_0104873 的抑制抑制了 BMSCs 的增殖和成骨分化。此外，机制测定还表明，circ_0104873 作为 microRNA-875-5p（miR-875-5p）的海绵体，上调了 Notch 受体 3（NOTCH3），从而激活了 Notch 信号通路。挽救测定表明，circ_0104873 通过靶向 miR-875-5p/NOTCH3 轴促进 OA 的发展。总之，circ_0104873 通过 miR-875-5p/NOTCH3/Notch 信号通路促进 OA 的进展，这可能为 OA 的治疗提供一个有前途的靶点。
