The inhibition of EZH2 ameliorates osteoarthritis development through the Wnt/β-catenin pathway

• DOI: 10.1038/srep29176
• Publication Date: 2016-08-19T11:24:03Z
• Authors: Linwei Chen; Yaosen Wu; Yan Wu; Ye Wang; Liaojun Sun; Fangcai Li
• Keywords: Chromatin immunoprecipitation

The purpose of our study was to elucidate the role histone methyltransferase enhancer zeste homologue 2 (EZH2) in pathophysiology osteoarthritis (OA) and develop a strategy modulate EZH2 activity for OA treatment. expression normal human cartilage compared by western blotting. effect overexpression inhibition on chondrocyte hypertrophy related gene examined real-time PCR, methylation promoter Wnt inhibitor SFRP1 analyzed using chromatin immunoprecipitation (ChIP) PCR. Histological assessment mice joint carried out assess vivo effects EPZ005687. We found level significantly increased chondrocytes patients humans. Overexpression promoted Indian Hedgehog, MMP-13, ADAMTS-5 COLX expression, while reversed this trend. Furthermore, induction led β-catenin signaling activation increasing H3K27me3 SFRP1, silenced signaling. Finally, intraarticular injection EPZ005687 delayed development mice. These results implicated development. Pharmacological may be an effective therapeutic approach osteoarthritis.