Orthopaedic Medical Center, The 2nd Hospital of Jilin University, Changchun, Jilin, P. R. China.
J Cell Biochem. 2019 Dec;120(12):19610-19620. doi: 10.1002/jcb.29267. Epub 2019 Jul 11.
Osteoarthritis (OA) is a common joint disease with high morbidity, but there is still no definitive treatment for it. Long noncoding RNAs (lncRNAs) have been confirmed to play key roles in OA progression. This work was done to investigate the roles and action mechanism of lncRNA TNFSF10 in OA. The messenger RNA levels of TNFSF10 in articular cartilage samples from patients or chondrocytes were detected by Quantitative real-time PCR assay (qRT-PCR). The effects of TNFSF10 on chondrocytes were evaluated on the basis of cell growth, apoptosis, and inflammation. Then, the interaction between TNFSF10 and miR-376-3p was explored by dual-luciferase reporter test, RNA-binding protein immunoprecipitation, and RNA pull-down assay. Finally, various cell experiments, Western blot analysis, and qRT-PCR were performed to study the interaction among TNFSF10, miR-376-3p, and fibroblast growth factor receptor 1 (FGFR1). It was found that TNFSF10 was upregulated in OA cartilages and stimulated cell proliferation, antiapoptosis, and inflammation for chondrocytes. In addition, TNFSF10 acted as a competing endogenous RNA to downregulate miR-376-3p, and the influence of TNFSF10 on chondrocytes was partly reversed by miR-376-3p. Moreover, FGFR1, as a target of miR-376-3p, had reversal functions on the outcomes mediated by miR-376-3p. The further analysis displayed that there was a negative relationship between TNFSF10 and miR-376-3p as well as miR-376-3p and FGFR1, while FGFR1 was positively related with TNFSF10. Altogether, TNFSF10 overexpression probably stimulated proliferation and inflammation, and inhibited apoptosis by regulating the miR-376-3p/FGFR1 axis, implying that its increase contributed to OA progression. Our study provided a new potential biomarker or therapeutic target-TNFSF10, which was helpful to develop an efficient approach to cure OA.
骨关节炎（OA）是一种常见的关节疾病，发病率高，但目前仍没有明确的治疗方法。长链非编码 RNA（lncRNA）已被证实在 OA 进展中发挥关键作用。本研究旨在探讨 lncRNA TNFSF10 在 OA 中的作用和作用机制。采用实时定量 PCR（qRT-PCR）检测患者关节软骨样本或软骨细胞中 TNFSF10 的信使 RNA 水平。基于细胞生长、凋亡和炎症，评估 TNFSF10 对软骨细胞的影响。然后，通过双荧光素酶报告基因检测、RNA 结合蛋白免疫沉淀和 RNA 下拉实验探讨 TNFSF10 与 miR-376-3p 的相互作用。最后，通过各种细胞实验、Western blot 分析和 qRT-PCR 研究 TNFSF10、miR-376-3p 和成纤维细胞生长因子受体 1（FGFR1）之间的相互作用。结果发现，OA 软骨中 TNFSF10 上调，并刺激软骨细胞增殖、抗凋亡和炎症。此外，TNFSF10 作为竞争性内源性 RNA 下调 miR-376-3p，miR-376-3p 部分逆转 TNFSF10 对软骨细胞的影响。此外，作为 miR-376-3p 的靶基因，FGFR1 对 miR-376-3p 介导的结果具有逆转作用。进一步分析显示，TNFSF10 与 miR-376-3p 以及 miR-376-3p 与 FGFR1 呈负相关，而 FGFR1 与 TNFSF10 呈正相关。总之，TNFSF10 过表达可能通过调节 miR-376-3p/FGFR1 轴刺激增殖和炎症，抑制凋亡，从而促进 OA 进展。本研究为开发有效的 OA 治疗方法提供了一个新的潜在生物标志物或治疗靶点-TNFSF10。
