Triclocarban triggers osteoarthritis via DNMT1-mediated epigenetic modification and suppression of COL2A in cartilage tissues

Yibo Zhang; Liu He; Yiqi Yang; Jieqiong Cao; Zijian Su; Bihui Zhang; Huiying Guo; Zhenyu Wang; Peiguang Zhang; Junye Xie; Jieruo Li; Jinshao Ye; Zhengang Zha; Hengyi Yu; An Hong; Xiaojia Chen

doi:10.1016/j.jhazmat.2023.130747

Triclocarban triggers osteoarthritis via DNMT1-mediated epigenetic modification and suppression of COL2A in cartilage tissues

J Hazard Mater. 2023 Apr 5:447:130747. doi: 10.1016/j.jhazmat.2023.130747. Epub 2023 Jan 7.

Authors

Yibo Zhang¹, Liu He¹, Yiqi Yang², Jieqiong Cao¹, Zijian Su¹, Bihui Zhang¹, Huiying Guo², Zhenyu Wang¹, Peiguang Zhang¹, Junye Xie¹, Jieruo Li², Jinshao Ye³, Zhengang Zha², Hengyi Yu⁴, An Hong⁵, Xiaojia Chen⁶

Affiliations

¹ Department of Cell Biology, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong Provincial biotechnology drug & Engineering Technology Research Center, Jinan University, Guangzhou 510632, China.
² The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
³ School of Environment, Jinan University, Guangzhou 510632, China.
⁴ Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
⁵ Department of Cell Biology, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong Provincial biotechnology drug & Engineering Technology Research Center, Jinan University, Guangzhou 510632, China.. Electronic address: tah@jnu.edu.cn.
⁶ Department of Cell Biology, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong Provincial biotechnology drug & Engineering Technology Research Center, Jinan University, Guangzhou 510632, China.. Electronic address: tchenxj@jnu.edu.cn.

PMID: 36680903
DOI: 10.1016/j.jhazmat.2023.130747

Abstract

Triclocarban (TCC) is a widely used environmental endocrine-disrupting chemical (EDC). Articular injury of EDCs has been reported; however, whether and how TCCs damage the joint have not yet been determined. Herein, we revealed that exposure to TCC caused osteoarthritis (OA) within the zebrafish anal fin. Mechanistically, TCC stimulates the expression of DNMT1 and initiates DNA hypermethylation of the type II collagen coding gene, which further suppresses the expression of type II collagen and other extracellular matrices. This further results in decreased cartilage tissue and narrowing of the intraarticular space, which is typical of the pathogenesis of OA. The regulation 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: Cartilage; Collagen; DNA methylation; Osteoarthritis; Triclocarban.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cartilage, Articular* / metabolism
Cartilage, Articular* / pathology
Collagen Type II / genetics
Collagen Type II / metabolism
DNA (Cytosine-5-)-Methyltransferase 1 / genetics
DNA (Cytosine-5-)-Methyltransferase 1 / metabolism
Epigenesis, Genetic
Humans
Osteoarthritis* / chemically induced
Osteoarthritis* / genetics
Osteoarthritis* / metabolism
Zebrafish / metabolism
Zebrafish Proteins / genetics

Substances

triclocarban
Collagen Type II
Dnmt1 protein, zebrafish
DNA (Cytosine-5-)-Methyltransferase 1
Zebrafish Proteins