and Suppress Synovial Inflammation and Proliferation in Rheumatoid Arthritis by Targeting

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial hyperplasia. and are homologous miRNAs with the same gene targeting spectrum. It is known that play an important role in protecting osteoarthritis development; however, the roles of in RA disease have not been determined. In the present study, we investigated the effects and molecular mechanisms of on synovial inflammation and hyperproliferation in RA. The effects of on the inflammation and abnormal proliferation in primary fibroblast-like synoviocytes (FLSs) were examined by gain-of-function and loss-of-function approaches in vitro and in vivo. We identified the structure-specific recognition protein 1 () as a downstream target gene of based on the bioinformatics analysis. We overexpressed and in FLS to determine the relationship between and and their effects on synovial hyperplasia. We created a collagen-induced arthritis (CIA) model in wild-type as well as double knockout (dKO) mice to induce RA phenotype and administered adeno-associated virus (AAV)-mediated - (AAV-) by intra-articular injection into dKO mice. We found that attenuated excessive cell proliferation and synovial inflammation in RA. was the downstream target gene of affected synovial proliferation and decelerated RA progression by targeting . CIA mice with deficiency displayed enhanced synovial hyperplasia and inflammation. RA phenotypes observed in deficient mice were significantly ameliorated by intra-articular delivery of AAV-, confirming the involvement of -signaling during RA development. In this study, we demonstrated that antagonize synovial hyperplasia and inflammation in RA by regulation of . may serve as novel agents to treat RA disease.