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

被引:15
作者
Zhang, Yibo [1 ]
He, Liu [1 ]
Yang, Yiqi [2 ]
Cao, Jieqiong [1 ]
Su, Zijian [1 ]
Zhang, Bihui [1 ]
Guo, Huiying [2 ]
Wang, Zhenyu [1 ]
Zhang, Peiguang [1 ]
Xie, Junye [1 ]
Li, Jieruo [2 ]
Ye, Jinshao [3 ]
Zha, Zhengang [2 ]
Yu, Hengyi [4 ]
Hong, An [1 ,5 ]
Chen, Xiaojia [1 ,5 ]
机构
[1] Jinan Univ, Guangdong Prov Biotechnol Drug & Engn Technol Res, Guangdong Prov Key Lab Bioengn Med, Dept Cell Biol,Coll Life Sci,Natl Engn Res Ctr Gen, Guangzhou 510632, Peoples R China
[2] Jinan Univ, Affiliated Hosp 1, Guangzhou 510630, Peoples R China
[3] Jinan Univ, Sch Environm, Guangzhou 510632, Peoples R China
[4] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Pharm, Wuhan 430030, Peoples R China
[5] Jinan Univ, Dept Cell Biol, 601 Huangpu Rd, Guangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
Triclocarban; Osteoarthritis; Cartilage; Collagen; DNA methylation; URINARY CONCENTRATIONS; ASSOCIATION; BONE; BENZOPHENONES; POPULATION; BISPHENOLS; TRICLOSAN;
D O I
10.1016/j.jhazmat.2023.130747
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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. Mechanisti-cally, 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 patho-genesis 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.
引用
收藏
页数:12
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