PHARMACOLOGICAL INHIBITION OF EZH2 SUPPRESSES PAIN IN MICE WITH MONOIODOACETATE-INDUCED OSTEOARTHRITIS BY REGULATING INFLAMMATION, OXIDATIVE STRESS, AND AUTOPHAGY IN SYNOVIAL CELLS.

Abstract

Purpose: Recently, we and others have shown that Enhancer of Zest Homolog 2 (EZH2), the major histone methyltransferase that catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), plays a major role in osteoarthritis (OA) progression by regulating chondrocytes hypertrophy and catabolism. However, whether EZH2 play a role in pain, which is the most common and disabling symptom of osteoarthritis is not yet known. Herein, we tested whether EZH2 inhibition could reduce pain in addition to OA progression in monoiodoacetate (MIA)-induced mice model of knee joint OA pain, and investigated the role of EZH2 in human OA synovial cells.