Overexpression of microRNA-1 controls the development of osteoarthritis via targeting FZD7 of Wnt/β-catenin signaling

Abstract

Purpose: Osteoarthritis (OA) is a common cause of functional deterioration in older adults and is an immense burden on the aging population. However, molecular mechanism underlying the regulation of OA in patients requires further elucidation, particularly with respect to the role of microRNAs. Thus, the present study was to investigate the expression level of miR-1 in OA and normal chondrocytes and to confirm whether overexpression miR-1 may inhibit the degradation of chondrocytes via targeting FZD7 of Wnt/β-catenin signaling. Methods: OA-related mRNA and miR-1 expression was analyzed using RT-PCR in OA and normal patients. CH8 chondrocytes were transfected with plasmid DNA, miR-1 agmir, miR-1 antagomir or agomir/ antagomir negative control. After transfection, RT-PCR was performed to examine gene expression levels of miR-1, matrix metallopeptidase 13 (MMP13), MMP-9, Bone Morphogenetic Protein 2 (BMP-2), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and type II collagen (COL2A1). Bioinformatics and luciferase reporter assay were conducted to confirm whether FZD7 was a target of miR-1. Wnt/β-catenin downstream signals and mRNA/protein expression were evaluated using Western blotting and RT-PCR. Results: A significant enrichment of miR-1 was found in OA tissue, not in normal patients, implying a key role of miR-1 in determining occurrence of OA. When overexpressed in CH8 cells, miR-1 inhibited the expression of key OA-related genes. Importantly, we found miR-1 inhibited degradation of chondrocytes by modulating the activities of Wnt/β-catenin signaling. FZD7 was confirmed as miR-1 targets using luciferase reporter assay. Conclusions: The present study demonstrated that overexpression of miR-1 inhibits degradation of chondrocytes by downregulation of FZD7 via suppressing WNT signaling pathway. These findings may suggest that miR-1 has an important role in the pathogenesis of OA and is a potential therapeutic target.