Inhibition of miR-199b-5p reduces pathological alterations in osteoarthritis by potentially targeting <i>Fzd6</i> and <i>Gcnt2</i>.

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-199b-5p. In vitro cell experiments demonstrated that miR-199b-5p inhibits chondrocyte vitality and promotes extracellular matrix degradation. Conversely, inhibition of miR-199b-5p under inflammatory conditions exhibited protective effects against damage. Local viral injection of miR-199b-5p into mice induced a decrease in pain threshold and OA-like changes. In an OA model, inhibition of miR-199b-5p alleviated the pathological progression of OA. Furthermore, bioinformatics analysis and experimental validation identified <i>Gcnt2</i> and <i>Fzd6</i> as potential target genes of <i>MiR-199b-5p</i>. Thus, these results indicated that <i>MiR-199b-5p</i>/<i>Gcnt2</i> and <i>Fzd6</i> axis might be a novel therapeutic target for the treatment of OA.