circRNA.33186 Contributes to the Pathogenesis of Osteoarthritis by Sponging miR-127-5p

• Published in: Molecular therapy Vol. 27; no. 3; pp. 531 - 541
• Main Authors: Zhou, Zhi-bin, Huang, Gao-xiang, Fu, Qiang, Han, Bin, Lu, Jia-jia, Chen, Ai-min, Zhu, Lei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.03.2019; Elsevier Limited; American Society of Gene & Cell Therapy
• Subjects: Age; Animals; Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Arthritis; Blotting, Western; Cartilage (articular); Cartilage diseases; Cell Proliferation - genetics; Cell Proliferation - physiology; Cells, Cultured; Chondrocytes; circRNA.33186; circular RNAs; Collagen; Collagen (type II); Collagen Type II - genetics; Collagen Type II - metabolism; Collagenase 3; Experiments; Flow cytometry; Fluorescent Antibody Technique; IL-1β; Immunoglobulins; Immunohistochemistry; Interleukin-1beta - metabolism; Male; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 13 - metabolism; Meniscus; Mice; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR-127-5p; Morphology; Original; Osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteoarthritis - pathology; Pathogenesis; Proteins; RNA, Circular - genetics; RNA, Circular - metabolism; Sclerosis; Statistical analysis; Subchondral bone; United Kingdom > UK; United States > US; circular RNAs; osteoarthritis; miR-127-5p; circRNA.33186
• DOI: 10.1016/j.ymthe.2019.01.006
• ISSN: 1525-0016; 1525-0024

Osteoarthritis (OA), the most prevalent age-related joint disorder, is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. Accumulating evidences indicate that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. Here we showed that circRNA.33186 was significantly upregulated in IL-1β)-treated chondrocytes and in cartilage tissues of a destabilized medial meniscus (DMM)-induced OA mouse model. Knockdown of circRNA.33186 increased anabolic factor (type II collagen) expression and decreased catabolic factor (MMP-13) expression. Knockdown of circRNA.33186 also promoted proliferation and inhibited apoptosis in IL-1β-treated chondrocytes. Silencing of circRNA.33186 in vivo markedly alleviated DMM-induced OA. Mechanistic study showed that circRNA.33186 directly binds to and inhibits miR-127-5p, thereby increasing MMP-13 expression, and contributes to OA pathogenesis. Taken together, our findings demonstrated a fundamental role of circRNA.33186 in OA progression and provide a potential drug target in OA therapy. Zhu and colleagues demonstrate that circRNA.33186 regulates chondrocyte functions, including ECM catabolism, proliferation, and apoptosis. Silencing of circRNA.33186 alleviated OA by acting as a sponge of miR-127-5p. These findings reveal a fundamental role of circRNA.33186 in OA progression and provide a potential drug target in OA therapy.