Yang Yang1, Yawei Wang2, Haobo Jia1, Bing Li1, Dan Xing3, Jiao Jiao Li4,5. 1. Department of Orthopaedics, Tianjin Hospital, Tianjin, China. 2. Department of Electromyography, Tianjin Hospital, Tianjin, China. 3. Arthritis Clinic & Research Center, Peking University People's Hospital, Peking University, Beijing, China. 4. Kolling Institute, Faculty of Medicine and Health, University of Sydney, St. Leonards, New South Wales, Australia. 5. School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Ultimo, New South Wales, Australia.
Abstract
OBJECTIVE: Osteoarthritis (OA) is an incurable joint disease characterized by pronounced pain. MicroRNAs constitute epigenetic mechanisms that may affect OA progression by contributing to changes in chondrocyte phenotype. This study investigates for the first time whether there is a link between miRNA-1 (miR-1) and OA pathogenesis, and the molecular mechanisms involved. DESIGN: OA-associated gene expression, including MMP-13, ADAMTS5, and COL2A1 was compared in chondrocytes from non-OA and OA cartilage, and in SW1353 cells over- and underexpressing miR-1. Bioinformatics and luciferase reporter assay were conducted to confirm whether FZD7 was a target of miR-1. The effects of miR-1 on FZD7 expression and downstream Wnt/β-catenin signalling were investigated. RESULTS: Non-OA and OA chondrocytes differed significantly in the expression of miR-1 and OA-associated genes. MiR-1 over- and underexpression in SW1353 cells, respectively, reduced and enhanced gene expression associated with cartilage catabolism. FZD7, which has an important role in the Wnt/β-catenin signaling pathway, was shown to be a potential target of miR-1. MiR-1 binding to FZD7 increased the levels of phosphorylated (inactivated) β-catenin, thereby preventing downstream β-catenin signaling. CONCLUSIONS: Inhibition of Wnt/β-catenin signaling by miR-1 in chondrocytes may attenuate the expression of genes that regulate the activity of catabolic enzymes. This finding may be useful for future investigations of molecular targets for OA treatment.
OBJECTIVE: Osteoarthritis (OA) is an incurable joint disease characterized by pronounced pain. MicroRNAs constitute epigenetic mechanisms that may affect OA progression by contributing to changes in chondrocyte phenotype. This study investigates for the first time whether there is a link between miRNA-1 (miR-1) and OA pathogenesis, and the molecular mechanisms involved. DESIGN: OA-associated gene expression, including MMP-13, ADAMTS5, and COL2A1 was compared in chondrocytes from non-OA and OA cartilage, and in SW1353 cells over- and underexpressing miR-1. Bioinformatics and luciferase reporter assay were conducted to confirm whether FZD7 was a target of miR-1. The effects of miR-1 on FZD7 expression and downstream Wnt/β-catenin signalling were investigated. RESULTS: Non-OA and OA chondrocytes differed significantly in the expression of miR-1 and OA-associated genes. MiR-1 over- and underexpression in SW1353 cells, respectively, reduced and enhanced gene expression associated with cartilage catabolism. FZD7, which has an important role in the Wnt/β-catenin signaling pathway, was shown to be a potential target of miR-1. MiR-1 binding to FZD7 increased the levels of phosphorylated (inactivated) β-catenin, thereby preventing downstream β-catenin signaling. CONCLUSIONS: Inhibition of Wnt/β-catenin signaling by miR-1 in chondrocytes may attenuate the expression of genes that regulate the activity of catabolic enzymes. This finding may be useful for future investigations of molecular targets for OA treatment.
Authors: C R Scanzello; E Umoh; F Pessler; C Diaz-Torne; T Miles; E Dicarlo; H G Potter; L Mandl; R Marx; S Rodeo; S R Goldring; M K Crow Journal: Osteoarthritis Cartilage Date: 2009-03-06 Impact factor: 6.576
Authors: Tung-Ying Lu; Bo Lin; Yang Li; Arshi Arora; Lu Han; Cheng Cui; Claudia Coronnello; Yi Sheng; Panayiotis V Benos; Lei Yang Journal: J Mol Cell Cardiol Date: 2013-08-09 Impact factor: 5.000
Authors: Tracey E Swingler; Guy Wheeler; Virginia Carmont; Hannah R Elliott; Matthew J Barter; Muhammad Abu-Elmagd; Simon T Donell; Raymond P Boot-Handford; Mohammad K Hajihosseini; Andrea Münsterberg; Tamas Dalmay; David A Young; Ian M Clark Journal: Arthritis Rheum Date: 2011-12-05