Shu Hu1, Guping Mao1, Ziji Zhang1, Peihui Wu1, Xingzhao Wen1, Weiming Liao2, Zhiqi Zhang3. 1. Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. 2. Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. Electronic address: liaowmsysu@163.com. 3. Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. Electronic address: zhzhiqi@mail.sysu.edu.cn.
Abstract
AIMS: 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. MATERIALS AND METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIMS: 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. MATERIALS AND METHODS: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. KEY FINDINGS: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. SIGNIFICANCE: 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.