NEAT1 attenuates osteoarthritis development by sponging miR-424-5p and up-regulating SMAD7 expression

Abstract Background: Osteoarthritis is extensively accepted as a chronic joint disease primarily characterized by destruction of articular cartilage, yet with rare molecular mechanism underlying its development and limited therapeutic targets in clinic. We here to investigate the role of NEAT1 and its molecular basis in OA development. Methods: Rat tissues and chondrocytes with osteoarthritis were used to detect the mRNA level of SMAD7 and miR-424-5p in which the correlation between them was also analyzed; Overexpression and knockdown of miRNA-424-5p were implemented to detect the regulation on SMAD7; The level of inflammatory factors and cell apoptosis of chondrocytes were detected with the opposite treatment on miR-424-5p; The potential interacting lncRNA was identified through online tool and RIP was employed to demonstrate the association between them; The biological coordination between NEAT1 and miR-425-5p in osteoarthritis was explored via the effects on inflammatory factors and cell apoptosis of chondrocytes. Results: Significantly, our results showed that levels of miR-424-5p are negatively correlated to expression of SMAD7 in rat cartilage tissues and chondrocytes, and overexpression of miR-424-5p was demonstrated to down-regulate SMAD7 expression. Additionally, the results also showed that miR-424-5p regulated expression of pro-inflammatory cytokines and apoptosis in chondrocytes via a SMAD7-dependent manner. Morever, the potential interacting lncRNA of miR-424-5p was figured out, and NEAT1 was proved to inversely mediate miR-424-5p expression leading to up-regulation of SMAD7. Further, NEAT1 was also estimated to work concert with miR-424-5p orchestrating expression of pro-inflammatory cytokines and chondrocytes apoptosis to ameliorate development of OA. Conclusions: We here demonstrate that NEAT1 could attenuate OA development via sponging miR-424-5p and thus up-regulating SMAD7 expression. Our data suggest that NEAT1-miR-424-5p-SMAD7 axis might be a potential therapeutic target for OA patients.