MicroRNA-320c inhibits development of osteoarthritis through downregulation of canonical Wnt signaling pathway

• Published in: Life sciences (1973) Vol. 228; pp. 242 - 250
• Main Authors: Hu, Shu, Mao, Guping, Zhang, Ziji, Wu, Peihui, Wen, Xingzhao, Liao, Weiming, Zhang, Zhiqi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.07.2019; Elsevier BV
• Subjects: 3' Untranslated regions; Adolescent; Adult; Aged; Aging; Antisense RNA; Arthritis; beta Catenin - genetics; beta Catenin - metabolism; Biocompatibility; Canonical Wnt signaling pathway; Cartilage; Cartilage diseases; Cells, Cultured; Chondrocytes; Chondrocytes - cytology; Chondrocytes - metabolism; Chondrogenesis; Collagen; Collagenase; Deformation mechanisms; Down-Regulation; Embryos; Female; Gene expression; Gene Expression Regulation; Genes; Humans; Hypertrophy; Male; MicroRNA-320c; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; Osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - metabolism; Pathogenesis; Ribonucleic acid; RNA; Signal transduction; Signaling; siRNA; Stem cell transplantation; Stem cells; Transcription; Wnt protein; Wnt Signaling Pathway; Young Adult; β-Catenin; MicroRNA-320c; Osteoarthritis; Canonical Wnt signaling pathway
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.05.011

Osteoarthritis (OA) is a leading cause of deformity in aging people. Emerging evidence suggests that microRNAs and Wnt signaling pathway are associated with its pathogenesis. We aimed to determine whether microRNA-320c inhibits the development of osteoarthritis by suppressing Wnt signaling pathway. MiR-320c and β-catenin expression was assessed in human adipose derived stem cells (hADSCs) model of chondrogenesis and in normal and OA primary human chondrocytes. OA chondrocytes were transfected with miR-320c or its antisense inhibitor and β-catenin siRNA respectively. Direct interaction between miR-320c and β-catenin mRNA as well as activity of β-catenin/TCF complex were confirmed by luciferase reporter assay. Mmu-miR-320-3p agomir was intra-articularly injected in collagenase-induced OA mouse model. OA progression was evaluated histologically and immunohistochemically. MiR-320c was decreased and β-catenin was increased in OA chondrocytes and late stage of hADSCs chondrogenesis. Overexpression of miR-320c and knockdown of β-catenin had similar effects that the cartilage-specific genes were elevated and hypertrophy-related genes were down-regulated in OA chondrocytes. Luciferase reporter assay confirm that miR-320c regulated the expression of β-catenin by directly targeting 3′UTR of β-catenin mRNA and decreased the relative transcriptional activity of the β-catenin/TCF complex. Injection of mmu-miR-320-3p attenuated OA progression in the OA mouse model. Our results supports that miR-320c can inhibits the degeneration of osteoarthritis chondrocytes via suppressing the canonical Wnt signaling pathway and indicates the potential of miR-320c as a novel therapeutic agent for osteoarthritis treatment.