Abstract

Object Osteoarthritis (OA) is a chronic and degenerative joint disorder that is prevalent in middle-aged and older populations. While several long non-coding RNAs (lncRNAs) have been implicated in OA progression, the role of lncRNA Mirt2 and its regulatory mechanisms remain unclear. Methods The expression of lncRNA Mirt2, miR-429, and TANK-binding kinase 1 (TBK1) was detected using qRT-PCR in normal and OA cartilage tissues. The interleukin (IL)−1β-stimulated chondrocyte was used as an in vitro OA cell. EdU, TUNEL assay, western blot, and ELISA assays were used for our experiments. Luciferase reporter assays, RNA immunoprecipitation (RIP), and RNA pulldown were used to investigate the interactions between lncRNA Mirt2, miR-429, and TBK1. An in vivo OA model was established, and cartilage damage was evaluated using H/E and Safranin O/Fast Green staining. Results LncRNA Mirt2 expression was significantly downregulated in OA cartilage tissues and IL-1β-stimulated chondrocytes ( p < 0.05). Transfection of the lncRNA Mirt2 overexpression vector led to a remarkable increase in cell proliferation, a significant reduction in cell apoptosis and inflammation, and a marked elevation in autophagy in IL-1β-induced chondrocytes ( p < 0.05). Functional investigation revealed that lncRNA Mirt2 acts as a competing endogenous RNA (ceRNA) by sponging miR-429 in IL-1β-induced chondrocytes. Additionally, miR-429 directly targets TBK1. Rescue experiments showed that overexpression of miR-429 or inhibition of TBK1 effectively counteracted the functional consequences of lncRNA Mirt2 upregulation in IL-1β-stimulated chondrocytes, reversing its promotive effects on cell proliferation and autophagy, as well as its inhibitory effect on apoptosis. The in vivo experiments indicated overexpression of lncRNA Mirt2 down-regulated miR-429, up-regulated TBK1, substantially attenuated cartilage damage, and accelerated autophagy in OA mice ( p < 0.05). Conclusion LncRNA Mirt2 promoted chondrocyte prol