Genes regulated by both of Ten-Eleven translocation 3 and Tumor necrosis factor α in Rheumatoid arthritis fibroblast-like synoviocytes

As DNA demethylation is a dynamic epigenetic regulation in pattern formation of DNA methylation, we reasoned that DNA demethylation facilitates Rheumatoid arthritis (RA) progression. To address this point, we picked up the DNA dioxygenase family members (Ten-Eleven translocation: TET1/2/3) as these enzymes conduct the prime process of DNA demethylaion. Tumor necrosis factor α (TNFα) , one of the pro-inflammatory cytokines, was found effective in up-regulation in TET3 level in the cultured fibroblast-like synoviocytes (FLS), and the stimulated FLS cells exhibited high cell mobility with gene induction of cell-migration related factors in a TET3-dependent manner. From our findings, we presume that DNA demethylation mediated TET3 facilitates RA progression and chronicity as an epigenetic regulation. To ask whether TET3 mediates the TNFα action in the gene expression program for the transformation of FLS, we used a gene microarray analysis to profile global gene regulation in the cultured RA FLS treated by TNFα, together with TET3 knockdown by small interfering RNA (siRNA).