PUBLICATION

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

Authors

Zhang, Y., He, L., Yang, Y., Cao, J., Su, Z., Zhang, B., Guo, H., Wang, Z., Zhang, P., Xie, J., Li, J., Ye, J., Zha, Z., Yu, H., Hong, A., Chen, X.

ID

ZDB-PUB-230122-32

Date

2023

Source

Journal of hazardous materials 447: 130747130747 (Journal)

Registered Authors

Keywords

Cartilage, Collagen, DNA methylation, Osteoarthritis, Triclocarban

MeSH Terms

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

(all 14)

PubMed

36680903 Full text @ J. Hazard. Mater.

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.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
adamts15a	mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint	RNA-Seq	Fig. 4
agrn	mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint	RNA-Seq	Fig. 4
bglap	mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint	RNA-Seq	Fig. 4
bglapl	mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint	RNA-Seq	Fig. 4
col1a1a	mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint	RNA-Seq	Fig. 4
col2a1a	mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint	RNA-Seq	Fig. 4
col2a1b	mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint	RNA-Seq	Fig. 4
col5a2b	mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint	RNA-Seq	Fig. 4
has1	mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint	RNA-Seq	Fig. 4
itga10	mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint	RNA-Seq	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin blood increased accumulation anal fin, abnormal	Fig. 1
mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin citrate metabolic process increased occurrence, abnormal	Fig. 3
mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin fatty acid biosynthetic process increased occurrence, abnormal	Fig. 3
mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin FHA domain binding increased occurrence, abnormal	Fig. 3
mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin gene expression involved in extracellular matrix organization increased process quality, abnormal	Fig. 4
mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint adamts15a expression increased amount, abnormal	Fig. 4
mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint agrn expression decreased amount, abnormal	Fig. 4
mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint bglap expression decreased amount, abnormal	Fig. 4
mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint bglapl expression decreased amount, abnormal	Fig. 4
mitfa^w2/w2	chemical treatment by environment: triclocarban	Adult	anal fin joint col1a1a expression decreased amount, abnormal	Fig. 4

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
a9		Complex	mpv17
w2		Point Mutation	mitfa

Human Disease / Model

Human Disease	Fish	Conditions	Evidence
osteoarthritis	mitfa^w2/w2	chemical treatment by environment: triclocarban	TAS

Sequence Targeting Reagents

Fish

Fish
mitfa^w2/w2

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Zhang et al., 2023 ZDB-PUB-230122-32 PMID:36680903

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

Zhang et al., 2023

ZDB-PUB-230122-32
PMID:36680903