Epigallocatechin gallate (EGCG) can epigenetically regulate the receptor of advanced glycation end products (RAGE) to ameliorate Osteoarthritis

Abstract

Epigallocatechin-3-O-gallate is natural phytochemical of green tea. RAGE upregulation promotes osteoarthritis (OA) progression. Herein, we revealed that EGCG can repress RAGE expression epigenetically to ameliorate OA. Firstly we found that RAGE expression was dose-dependently reduced by EGCG on chondrocyte cell C28/I2. EGCG also suppressed RAGE in human primary OA chondrocytes, and accordingly attenuated ROS production and NF-κb activity. Osteoarthritic microenvironment was also improved by EGCG, which was reflected by the enhanced chondrogenic markers and reduced inflammatory markers. EGCG-induced ameliorations were counteracted by artificial overexpression of RAGE. Additionally, EGCG modulates RAGE expression not only by its antioxidant activity, but also by facilitating RAGE promoter hypermethylation. To confirm this epigenetic modification, we employed dCAS9-Tet1 against EGCG’s epigenetic regulation. RAGE level was correspondingly rescued after EGCG-induced hypermethylation status were blocked. These findings support therapeutic roles of EGCG on OA and uncover the novel molecular mechanism of EGCG-mediated RAGE modulation.

Keywords

• EGCG
• RAGE
• Osteoarthritis
• DNA methylation
• Epigenetic regulation