2016 Fiscal Year Final Research Report
Dynamism of DNA methylation in Rheumatoid Arthritis
| Project/Area Number |
26461479
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 関節リウマチ / エピジェネティクス / DNAメチル化 / 滑膜細胞 |
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| Outline of Final Research Achievements |
Discovery of the mechanism of active demethylation by TET proteins has rapidly advanced understanding of DNA methylation dynamism. Here, we demonstrate that TET3 is induced by inflammatory cytokine stimulation, and plays an important role in joint destruction in rheumatoid arthritis (RA). Arthritis was induced in C57BL/6 wild type and TET3 heterozygous-deficient (TET3+/-) mice with K/BxN serum. The arthritis score and bone erosion score were significantly decreased in the TET3+/- mice. In RA patient-derived fibroblast-like synoviocytes (FLS), the TET3 expression and 5-hydroxymethylcytosine levels were significantly increased by TNF stimulation. In addition, TET3 knockdown inhibited the TNF-induced production of CCL2 and ICAM-1 in RA FLS. These results suggest that continuous exposure to inflammatory cytokines results in leaving an inflammatory memory in FLS in a TET3-dependent manner, thereby promoting pannus formation and increasing the probability of joint destruction.
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| Free Research Field |
リウマチ学
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