Department of Orthopedics, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China.
Cell Cycle. 2021 Jun;20(11):1052-1066. doi: 10.1080/15384101.2021.1919838. Epub 2021 May 4.
The relevance of circular RNAs (circRNAs) has been indicated in the progression of various diseases. Nevertheless, the precise function of circRNAs in osteoarthritis (OA) remains to be established. Therefore, we aimed to investigate changes in the expression of a specific circRNA, hsa_circ_0134111 (circ_PDE1C) and predict its functions in OA. A rat model of OA was constructed to detect circ_PDE1C expression in knee joint tissues. Subsequently, CHON-001 chondrocytes were treated with IL-1β to mimic OA . circ_PDE1C was significantly overexpressed in knee cartilage tissues from OA patients relative to amputation patients. Knockdown of circ_PDE1C inhibited extracellular matrix (ECM) degradation and chondrocyte apoptosis. Furthermore, circ_PDE1C could target miR-224-5p, and miR-224-5p expressed poorly in knee cartilage tissues from OA patients. Overexpression of miR-224-5p inhibited ECM degradation and apoptosis in chondrocytes. miR-224-5p also targeted CCL2, which activated the JAK2/STAT signaling pathway, thereby promoting cartilage degradation and exacerbating the symptoms of OA patients. In conclusion, our findings underscore a novel role of circ_PDE1C in OA pathogenesis and suggest that targeting circ_PDE1C/miR-224-5p/CCL2 axis might provide an attractive approach for OA therapy.
环状 RNA（circRNAs）的相关性已在多种疾病的进展中得到证实。然而，circRNAs 在骨关节炎（OA）中的确切功能仍有待确定。因此，我们旨在研究特定 circRNA，hsa_circ_0134111（circ_PDE1C）的表达变化，并预测其在 OA 中的功能。构建了 OA 大鼠模型以检测膝关节组织中 circ_PDE1C 的表达。随后，用 IL-1β处理 CHON-001 软骨细胞以模拟 OA。与截肢患者相比，OA 患者膝关节软骨组织中 circ_PDE1C 显著过表达。circ_PDE1C 的敲低抑制了细胞外基质（ECM）降解和软骨细胞凋亡。此外，circ_PDE1C 可以靶向 miR-224-5p，而 OA 患者膝关节软骨组织中 miR-224-5p 表达不佳。miR-224-5p 的过表达抑制了软骨细胞的 ECM 降解和凋亡。miR-224-5p 还靶向 CCL2，后者激活 JAK2/STAT 信号通路，从而促进软骨降解并加重 OA 患者的症状。总之，我们的研究结果强调了 circ_PDE1C 在 OA 发病机制中的新作用，并表明靶向 circ_PDE1C/miR-224-5p/CCL2 轴可能为 OA 治疗提供一种有吸引力的方法。
