Circular RNA circANKRD36 regulates Casz1 by targeting miR‐599 to prevent osteoarthritis chondrocyte apoptosis and inflammation

• Published in: Journal of cellular and molecular medicine 2021-01, Vol.25 (1), p.120-131
• Main Authors: Zhou, Jian‐Lin, Deng, Shuang, Fang, Hong‐Song, Du, Xian‐jin, Peng, Hao, Hu, Qiong‐jie
• Format: Article
• Language: English
• Subjects: Aging; Apoptosis; Arthritis; Binding sites; Cartilage; Cartilage (articular); Cartilage diseases; Casz1; Chondrocytes; circANKRD36; Circular RNA; Cytokines; Flow cytometry; Hybridization; Inflammation; Inflammatory diseases; Investigations; MicroRNAs; miR‐599; Original; Osteoarthritis; Ribonucleic acid; RNA; Software; Statistical analysis
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15884

Osteoarthritis (OA) is an ageing‐related disease characterized by articular cartilage degradation and joint inflammation. circRNA has been known to involve in the regulation of multiple inflammatory diseases including OA. However, the mechanism underlying how circRNA regulates OA remains to be elucidated. Here, we report circANKRD36 prevents OA chondrocyte apoptosis and inflammation by targeting miR‐599, which specifically degrades Casz1. We performed circRNA sequencing in normal and OA tissues and found the expression of circANKRD36 is decreased in OA tissues. circANKRD36 is also reduced in IL‐1β–treated human chondrocytes. FACS analysis and Western blot showed that the knockdown of circANKRD36 promotes the apoptosis and inflammation of chondrocytes in IL‐1β stress. We then found miR‐599 to be the target of circANKRD36 and correlate well with circANKRD36 both in vitro and in vivo. By database analysis and luciferase assay, Casz1 was found to be the direct target of miR‐599. Casz1 helps to prevent apoptosis and inflammation of chondrocytes in response to IL‐1β. In conclusion, our results proved circANKRD36 sponge miR‐599 to up‐regulate the expression of Casz1 and thus prevent apoptosis and inflammation in OA.