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Dynamism of DNA methylation in Rheumatoid Arthritis

Research Project

Project/Area Number 26461479
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

Nakano Kazuhisa  産業医科大学, 医学部, 講師 (50406500)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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 / 炎症性サイトカイン / DNA脱メチル化
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.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (14 results)

All 2017 2016 2015 2014

All Journal Article (1 results) Presentation (11 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] 関節リウマチ滑膜におけるDNAメチル化とTET分子2017

    • Author(s)
      中野和久、田中良哉
    • Journal Title

      Keynote R・A

      Volume: 5 Pages: 9-13

    • Related Report
      2016 Annual Research Report
  • [Presentation] The epigenetic induction of aggressive phenotype of fibroblast-like synovial cells (FLS) in rheumatoid arthritis (RA), the role of DNA demethylation enzyme TET32016

    • Author(s)
      Kazuhisa Nakano, Akio Kawabe, Kei Sakata, Kaoru Yamagata, Shingo Nakayamada, Yoshiya Tanaka.
    • Organizer
      第8回国際関節リウマチフォーラム
    • Place of Presentation
      品川プリンスホテル(東京)
    • Year and Date
      2016-10-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 持続的炎症刺激による線維芽細胞様滑膜細胞(FLS)の表現型変化におけるDNA脱メチル化酵素TET3の役割とTET3阻害による関節炎制御2016

    • Author(s)
      河邊明男、中野和久、山形薫、阪田圭、中山田真吾、田中良哉
    • Organizer
      第44回日本臨床免疫学会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 炎症性サイトカインはリウマチ滑膜細胞にDNA脱メチル化酵素TET3依存性に骨・軟骨破壊を促進する2016

    • Author(s)
      河邊明男、中野和久、山形薫、阪田圭、中山田真吾、田中良哉
    • Organizer
      第34回日本骨代謝学会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] 関節リウマチ滑膜細胞は炎症性サイトカイン誘導性のDNA脱メチル化酵素TET3を介して骨・軟骨破壊を促進する2016

    • Author(s)
      河邊明男、中野和久、山形薫、阪田圭、中山田真吾、田中良哉
    • Organizer
      第2回日本骨免疫学会
    • Place of Presentation
      ホテルモントレ沖縄スパ&リゾート(沖縄)
    • Year and Date
      2016-07-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 持続的炎症刺激による線維芽細胞様滑膜細胞(FLS)の表現型変化におけるDNA脱メチル化酵素TET3の役割とTET3阻害による関節炎制御2016

    • Author(s)
      河邊明男、中野和久、山形薫、阪田圭、中山田真吾、田中良哉
    • Organizer
      第37回日本炎症・再生医学会
    • Place of Presentation
      みやこめっせ(京都)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 持続的炎症刺激による滑膜細胞の表現型変化におけるDNA脱メチル化酵素TET3の役割とTET3阻害による関節炎制御2016

    • Author(s)
      河邊明男、中野和久、山形薫、阪田圭、中山田真吾、田中良哉
    • Organizer
      第60回日本リウマチ学会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Alteration of DNA methylation by pro-inflammatory cytokines in Rheumatoid arthritis fibroblast-like synoviocytes2015

    • Author(s)
      Kazuhisa Nakano, Akio Kawabe, Kaoru Yamagata, Shingo Nakayamada, and Yoshiya Tanaka
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] RA滑膜の慢性炎症はDNA脱メチル化酵素Tet3依存性に滑膜細胞に攻撃的表現型を付与する2015

    • Author(s)
      中野和久、河邊明男、山形薫、中山田真吾、田中良哉
    • Organizer
      第1回日本骨免疫学会
    • Place of Presentation
      ホテルブリーズベイマリーナ(沖縄県宮古島市)
    • Year and Date
      2015-06-30
    • Related Report
      2015 Research-status Report
  • [Presentation] TET3-mediated epigenetic alteration in Rheumatoid arthritis fibroblast-like synoviocytes2015

    • Author(s)
      中野和久
    • Organizer
      第59回日本リウマチ学会
    • Place of Presentation
      名古屋国際会議場(愛知県(名古屋市))
    • Year and Date
      2015-04-25
    • Related Report
      2014 Research-status Report
  • [Presentation] TET3-mediated epigenetic alteration in Rheumatoid arthritis fibroblast-like synoviocytes2015

    • Author(s)
      Kazuhisa Nakano, Kaoru Yamagata, Shingo Nakayamada, Akio Kawabe, and Yoshiya Tanaka
    • Organizer
      第59回日本リウマチ学会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report
  • [Presentation] The Role Of TET3-Mediated DNA Demethylation By Pro-Inflammatory Cytokines In Rheumatoid Arthritis2014

    • Author(s)
      Kazuhisa Nakano
    • Organizer
      ACR /ARHP annual meeting 2014
    • Place of Presentation
      Boston Convention & Exhibition Center(ボストン/米国)
    • Year and Date
      2014-10-27
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 関節炎の予防・治療剤、検査キット、並びに関節炎予防・治療薬のスクリーニング方法2015

    • Inventor(s)
      中野和久
    • Industrial Property Rights Holder
      学校法人産業医科大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-08-24
    • Related Report
      2015 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 関節炎の予防・治療剤、検査キット、並びに関節炎予防・治療薬のスクリーニング方法2014

    • Inventor(s)
      中野和久
    • Industrial Property Rights Holder
      学校法人産業医科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-174638
    • Filing Date
      2014-08-28
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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