In:
Arthritis Research & Therapy, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2022-09-16)
Abstract:
Rheumatoid arthritis (RA) patients present with abnormal methylation patterns in their fibroblast-like synoviocytes (FLS). Given that DNA demethylation is critical for producing DNA methylation patterns, we hypothesized that DNA demethylation may facilitate RA progression. Therefore, we designed this study to examine the role of DNA dioxygenase family, Ten-Eleven translocation (TET1/2/3), in the pathological process of RA. Methods Synovial tissues and FLS were obtained from patients with RA and Osteoarthritis. K/BxN serum-induced arthritis was induced in Wild-type (WT) and TET3 heterozygous-deficient ( TET3 +/− ) C57BL/6 mice. Results We found that both TET3 and 5-hydroxymethylcytosine (5hmC) were upregulated in synovitis tissues from RA patients and confirmed this upregulation in the cultured FLS derived from synovitis tissues. Tumor necrosis factor α (TNFα) upregulated TET3 and 5hmC levels in cultured FLS, and the stimulated FLS exhibited high cell mobility with increased transcription of cellular migration-related factors such as C-X-C motif chemokine ligand 8 (CXCL8) and C-C motif chemokine ligand 2 (CCL2) in a TET3-dependent manner. In addition, TET3 haploinsufficiency lowered RA progression in a mouse model of serum-induced arthritis. Conclusions Based on these findings, we can assume that TET3-mediated DNA demethylation acts as an epigenetic regulator of RA progression.
Type of Medium:
Online Resource
ISSN:
1478-6362
DOI:
10.1186/s13075-022-02908-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2041668-4
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