Upregulation of long noncoding TNFSF10 contributes to osteoarthritis progression through the miR-376-3p/FGFR1 axis.

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.