Department of Orthopedics, The Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Department of Orthopedics District 1, The People's Hospital of Zhaoyuan City, Zhaoyuan, Shandong, China.
Bioengineered. 2022 Apr;13(4):8407-8418. doi: 10.1080/21655979.2022.2048773.
Circular RNAs (circRNAs) can regulate the progression of osteoarthritis (OA) via serving as competing endogenous RNAs (ceRNAs). This work was performed for functional research of circ_0005526 in Interleukin-1β (IL-1β)-induced OA injury. Circ_0005526, microRNA-142-5p (miR-142-5p) or transcription factor 4 (TCF4) expression was measured via reverse transcription-quantitative polymerase chain reaction assay. Cell analysis was performed by Cell Counting Kit-8 assay for cell viability, EdU assay for cell proliferation and flow cytometry for cell apoptosis. The protein level detection was conducted using western blot. Target analysis was carried out via dual-luciferase reporter assay and RNA pull-down assay. Circ_0005526 was upregulated in OA cartilage tissues and IL-1β-exposed chondrocyte cells. IL-1β inhibited cell viability and proliferation but enhanced cell apoptosis and inflammation, then these damages were attenuated after downregulation of circ_0005526. Circ_0005526 interacted with miR-142-5p, and circ_0005526 knockdown suppressed IL-1β-induced OA progression through upregulating miR-142-5p. TCF4 was regulated by circ_0005526 via targeting miR-142-5p. The function of circ_0005526 was also achieved by upregulation of TCF4. These results unraveled that circ_0005526 promoted IL-1β-induced chondrocyte injury in OA via suppressing miR-142-5p binding to TCF4.
环状 RNA(circRNAs)可以作为竞争性内源性 RNA(ceRNAs)来调节骨关节炎(OA)的进展。本研究旨在研究白细胞介素-1β(IL-1β)诱导 OA 损伤中 circ_0005526 的功能。通过逆转录定量聚合酶链反应试验测量 circ_0005526、microRNA-142-5p(miR-142-5p)或转录因子 4(TCF4)的表达。通过细胞计数试剂盒-8 检测细胞活力、EdU 检测细胞增殖和流式细胞术检测细胞凋亡来进行细胞分析。使用 Western blot 进行蛋白水平检测。通过双荧光素酶报告基因检测和 RNA 下拉实验进行靶标分析。OA 软骨组织和 IL-1β 暴露的软骨细胞中 circ_0005526 上调。IL-1β 抑制细胞活力和增殖,但增强细胞凋亡和炎症,下调 circ_0005526 后这些损伤减轻。circ_0005526 与 miR-142-5p 相互作用,circ_0005526 下调通过上调 miR-142-5p 抑制 IL-1β 诱导的 OA 进展。TCF4 受 circ_0005526 调控,通过靶向 miR-142-5p。circ_0005526 通过上调 TCF4 也实现了其功能。这些结果表明,circ_0005526 通过抑制 miR-142-5p 与 TCF4 的结合,促进了 IL-1β 诱导的 OA 软骨细胞损伤。