Triclocarban Triggers Osteoarthritis Via Dnmt1-Mediated Epigenetic Modification and Suppression of Col2a in Cartilage Tissues

Abstract

Triclocarban (TCC) is one of the wildly used environmental endocrine-disrupting chemicals (EDCs). The articular injury of EDCs has been issued; however, it has yet to be clarified whether and how TCC damage the joint. Herein, we uncovered that exposure to TCC caused osteoarthritis (OA) within zebrafish anal fin. Mechanistically, TCC stimulates the expression of DNMT1 and initiates the DNA hypermethylation of the type II collagen coding gene, which further suppresses the expression of type II collagen and other extracellular matrixes. This further results in decreased cartilage tissue and the narrowing of intraarticular space, typical pathogenesis of OA. The regulatory of OA occurrence by TCC is conserved between zebrafish cartilage tissue and human chondrocytes. Our findings clarified the hazard and potential mechanisms of TCC towards articular health and highlighted DNMT1 as a potential therapeutic target for OA caused by TCC.

Keywords: Triclocarban, osteoarthritis, cartilage, collagen, DNA methylation