Inhibition of miR-199b-5p reduces pathological alterations in Osteoarthritis by tar-geting Fzd6 and Gcnt2

Abstract

Osteoarthritis (OA) is a degenerative disease with a high prevalence in the elderly population, but our understanding of its mechanisms remains incomplete. Analysis of serum exosomal small RNA sequencing data from clinical patients and gene expression data from OA patient serum and cartilage obtained from the GEO database revealed a common dysregulated miRNA, miR-NA-199b-5p. In vitro cell experiments demonstrated that miRNA-199b-5p inhibits chondrocyte vitality and promotes extracellular matrix degradation. Conversely, inhibition of miRNA-199b- 5p under inflammatory conditions exhibited protective effects against damage. Local viral injec-tion of miRNA-199b-5p into mice induced a decrease in pain threshold and OA-like changes. In an OA model, inhibition of miRNA-199b-5p alleviated the pathological progression of OA. Fur-thermore, bioinformatics analysis and experimental validation identified Gcnt2 and Fzd6 as tar-get genes of miRNA-199b-5p. Thus, these results indicated that miRNA-199b-5p/Gcnt2 and Fzd6 axis might be a novel therapeutic target for the treatment of OA.