LincRNA-EPS Alleviates Inflammation in TMJ Osteoarthritis by Binding to SRSF3

Abstract

Temporomandibular joint osteoarthritis (TMJOA) is a common inflammatory disease that can cause pain, cartilage degradation, and subchondral bone loss. However, the key regulatory factors and new targets for the treatment of TMJOA have yet to be determined. Long noncoding RNAs (lncRNAs) have shown remarkable potential in regulating tissue homeostasis and disease development. The long intergenic RNA–erythroid prosurvival (lincRNA-EPS) is reported to be an effective inhibitor of inflammation, but its role in TMJOA is unexplored. Here, we found that lincRNA-EPS is downregulated and negatively correlated with inflammatory factors in the condyles of TMJOA mice. LincRNA-EPS knockout aggravated inflammation and tissue destruction after TMJOA modeling. The in vitro studies confirmed that loss of lincRNA-EPS facilitated inflammatory factor expression in condylar chondrocytes, while recovered expression of lincRNA-EPS showed anti-inflammatory effects. Mechanistically, RNA sequencing revealed that the inflammatory response pathway nuclear factor–kappa B (NF-κB) was mostly affected by lincRNA-EPS deficiency. Moreover, lincRNA-EPS was proved to effectively bind to serine/arginine-rich splicing factor 3 (SRSF3) and inhibit its function in pyruvate kinase isoform M2 (PKM2) formation, thus restraining the PKM2/NF-κB pathway and the expression of inflammatory factors. In addition, local injection of the lincRNA-EPS overexpression lentivirus significantly alleviated inflammation, cartilage degradation, and subchondral bone loss in TMJOA mice. Overall, lincRNA-EPS regulated the inflammatory process of condylar chondrocytes by binding to SRSF3 and showed translational application potential in the treatment of TMJOA.