MiR-582-3p alleviates osteoarthritis progression by targeting YAP1. (December 2020)

• Record Type: Journal Article
• Authors: He, Jun; Su, Xiaotao; Xie, Wenwei
• Is Part Of: Molecular immunology. Volume 128(2020:Dec.)
• Page Start: 258
• Page End: 267
• Publication Date: 2020-12
• Subjects: miR-582-3p -- YAP1 -- Osteoarthritis; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2020.10.022
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: YAP1 is upregulated in OA chondrocytes from rats. MiR-582-3p alleviates regulates cell apoptosis, inflammatory responses and ECM homeostasis in OA rat chondrocytes and C28/I2 cells. MiR-582-3p can bind with the 3′UTR of YAP1. YAP1 reverses miR-582-3p-mediated cell apoptosis, inflammatory responses and ECM homeostasis in OA rat chondrocytes and C28/I2 cells. MiR-582-3p suppresses OA development via targeting YAP1 in vivo. Abstract: Osteoarthritis (OA) is a widespread degenerative joint disease that affects more than 350 million people worldwide. Although YAP1 has been proved to play a key role in OA, the biological function and mechanism of YAP1 in OA still need further investigation. In the present study, we demonstrated that YAP1 was highly expressed in OA rat chondrocytes. Recently, growing microRNAs (miRNAs) have been reported to play important roles in OA development. Among them, miR-582-3p is one of the few significantly downregulated miRNAs and attracted our attention. Functional investigations indicated that miR-582-3p inhibited chondrocyte apoptosis, reduced the proinflammatory cytokine production and suppressed extracellular matrix (ECM) degradation. Subsequently, molecular mechanism exploration implied that YAP1 is a downstream target of miR-582-3p. Furthermore, rescue assays revealed that YAP1 amplification can reverse miR-582-3p mimic-mediated effects on chondrocyte apoptosis, inflammatory response, and ECM degradation. Moreover, the OA rat model was established to explore the function of miR-582-3p/YAP1 axis in vivo. The results showed that YAP1 overexpression can recover the effects induced by injection of AAV-miR-582-3p mimic on OA progression. To sum up, these findings implied a crucial role of miR-582-3p/YAP1 axis in OA, which may provide a promising therapeutic strategy for OA.