Triclocarban triggers osteoarthritis via DNMT1-mediated epigenetic modification and suppression of COL2A in cartilage tissues
Triclocarban triggers osteoarthritis via DNMT1-mediated epigenetic modification and suppression of COL2A in cartilage tissues
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Triclocarban 通过 DNMT1 介导的表观遗传修饰和软骨组织中 COL2A 的抑制引发骨关节炎
DOI：
10.1016/j.jhazmat.2023.130747
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发表时间：
2023-01-19
影响因子：
13.6
通讯作者：
Chen，Xiaojia
中科院分区：
文献类型：
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作者：
Zhang，Yibo;He，Liu;Chen，Xiaojia
三氯卡班（TCC）是一种广泛使用的环境内分泌干扰物（EDC）。内分泌干扰物对关节的损伤已有报道;然而，TCC是否以及如何损伤关节尚未确定。在此，我们发现，暴露于TCC引起骨关节炎（OA）在斑马鱼的臀鳍。从机制上讲，TCC刺激DNMT 1的表达并启动II型胶原蛋白编码基因的DNA超甲基化，这进一步抑制II型胶原蛋白和其他细胞外基质的表达。这进一步导致软骨组织减少和关节内空间变窄，这是OA的典型发病机制。TCC对OA发生的调节在斑马鱼软骨组织和人软骨细胞之间是保守的。我们的研究结果阐明了TCC对关节健康的危害和潜在机制，并强调DNMT 1是TCC引起的OA的潜在治疗靶点。
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.