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The development of novel therapeutic drug for periontitis targeting epgenetic regulation of TLR2

Research Project

Project/Area Number 16K20675
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Periodontology
Research InstitutionKyushu University

Principal Investigator

Tanaka Urara  九州大学, 大学病院, 助教 (50734993)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsDecitabine / 歯周炎モデルマウス / DNAメチル化 / 歯周炎 / TLR2 / エピジェネティックス / P. gingivalis
Outline of Final Research Achievements

The purpose of this study was to develop a novel therapeutic drug for periodontitis targeting epigenetics.
We observed severe bone loss in the ligature induced periodontitis model in mice and Decitabine significantly inhibited the bone loss. We found that the treatment with Decitabine significantly reduced osteoclasts both in vivo and in vitro and up-regulated the anti-inflammatory cytokines (IL-10 and TGF-β) in vitro. Next, we focused on Kruppel-like Factor 2 (KLF2) which is a transcription factor regulating inflammation. As the results, Decitabine increased KLF2 and KLF2 up-regulated the transcriptional activity of CCAAT/enhancer binding protein beta (CEBPB) and the anti-inflammatory cytokines IL-10 and TGF-β. We concluded that Decitabine inhibits alveolar bone loss by limiting osteoclastogenesis in mice and shows KLF2 can regulate that. Taken together, Decitabine may have utility in treating chronic inflammatory periodontal disease in humans.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 7 results)

  • [Journal Article] Amelogenin induces M2 macrophage polarisation via PGE2/cAMP signalling pathway2017

    • Author(s)
      Yamamichi Kensuke、Fukuda Takao、Sanui Terukazu、Toyoda Kyosuke、Tanaka Urara、Nakao Yuki、Yotsumoto Karen、Yamato Hiroaki、Taketomi Takaharu、Uchiumi Takeshi、Nishimura Fusanori
    • Journal Title

      Archives of Oral Biology

      Volume: 83 Pages: 241-251

    • DOI

      10.1016/j.archoralbio.2017.08.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of serum in innate immune responses of human leukocytes to synthetic lipopeptide2017

    • Author(s)
      Sanui Terukazu、Takeshita Masaaki、Fukuda Takao、Tanaka Urara、Alshargabi Rehab、Aida Yoshitomi、Nishimura Fusanori
    • Journal Title

      International Immunopharmacology

      Volume: 50 Pages: 61-68

    • DOI

      10.1016/j.intimp.2017.06.006

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adhesion attenuates respiratory burst induced by different modes of triggering in resting or LPS-primed neutrophils2017

    • Author(s)
      Sanui Terukazu、Takeshita Masaaki、Fukuda Takao、Tanaka Urara、Alshargabi Rehab、Aida Yoshitomi、Nishimura Fusanori
    • Journal Title

      Immunobiology

      Volume: 222 Issue: 8-9 Pages: 865-871

    • DOI

      10.1016/j.imbio.2017.05.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microarray Analysis of the Effects of Amelogenin on U937 Monocytic Cells2017

    • Author(s)
      Sanui Terukazu、Fukuda Takao、Yamamichi Kensuke、Toyoda Kyosuke、Tanaka Urara、Yotsumoto Karen、Taketomi Takaharu、Nishimura Fusanori
    • Journal Title

      American Journal of Molecular Biology

      Volume: 07 Issue: 02 Pages: 107-122

    • DOI

      10.4236/ajmb.2017.72009

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Investigation of the functional role of human Interleukin-8 gene haplotypes by CRISPR/Cas9 mediated genome editing.2016

    • Author(s)
      Manjunatha R. Benakanakere, Livia S. Finoti, Urara Tanaka, Gregory R. Grant, Raquel M. Scarel-Caminaga and Denis F. Kinane
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 31180-31180

    • DOI

      10.1038/srep31180

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Decitabine inhibits osteoclastogenesis and ameliorates periodontal bone loss in mice2017

    • Author(s)
      Urara Tanaka, Livia Finoti, Fusanori Nishimura, Denis F. Kinane and Manju Benakanakere
    • Organizer
      95th General Session & Exhibition of the International Association for Dental Research
    • Place of Presentation
      Moscone West Convention Center, San Francisco,USA
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of Decitabine on Osteoclastogenesis and Periodontal Bone loss in Mice2017

    • Author(s)
      Urara Tanaka, Manju Benakanakere, Denis Kinane and Fusanori Nishimura
    • Organizer
      頭脳循環2nd Symposium
    • Place of Presentation
      福岡リーセントホテル、福岡市
    • Year and Date
      2017-02-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 歯周炎モデルマウスにおける歯槽骨吸収及び破骨細胞分化へのDecitabineの効果2017

    • Author(s)
      田中 麗
    • Organizer
      日本歯科保存学会2017年度春季学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Microarray Analysis of U937 Monocytic Cells Stimulated with Amelogenin.2017

    • Author(s)
      Urara Tanaka
    • Organizer
      Penn Periodontal Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Decitabineによる歯周炎モデルマウスにおける歯槽骨吸収抑制効果の検討2016

    • Author(s)
      田中麗、讃井彰一、福田隆男、西村英紀
    • Organizer
      第59回秋季日本歯周病学会学術大会
    • Place of Presentation
      朱鷺メッセ、新潟市
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Decitabine (5-aza-2'-deoxycytidine) Ameliorates Periodontal Bone loss2016

    • Author(s)
      田中 麗, M Benakanakere, Denis F. Kinane,
    • Organizer
      94th General Session & Exhibition of the International Association for Dental Research
    • Place of Presentation
      COEX Convention&Exhibition Center, Seoul,Korea
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Spry2 Downregulation Shifts Macrophages Toward an M2 Phenotype by Stimulation with Interferon γ and Porphyromonas Gingivalis Lipopolysaccharide.2016

    • Author(s)
      讃井 彰一, 福田 隆男, 田中 麗, 豊田 敬介, 山道 研介, 武富 孝治, 西村 英紀,
    • Organizer
      94th General Session & Exhibition of the International Association for Dental Research
    • Place of Presentation
      COEX Convention&Exhibition Center, Seoul,Korea
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Grp78 is Crucial for Cell Migration Induced by Amelogenin in a Human Periodontal Ligament Cells2016

    • Author(s)
      豊田 敬介, 福田 隆男, 讃井 彰一, 田中 麗, 山道 研介, 武富 孝治, 西村 英紀
    • Organizer
      94th General Session & Exhibition of the International Association for Dental Research
    • Place of Presentation
      COEX Convention&Exhibition Center, Seoul,Korea
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Amelogenin Modulates Macrophage Phenotype During Inflammatory Responses2016

    • Author(s)
      山道 研介, 福田 隆男, 讃井 彰一, 豊田 敬介, 田中 麗, 武富 孝治, 西村 英紀
    • Organizer
      94th General Session & Exhibition of the International Association for Dental Research
    • Place of Presentation
      COEX Convention&Exhibition Center, Seoul,Korea
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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