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Development of a novel drug for periodontitis based on the characteristics of gingival epithelial cells

Research Project

Project/Area Number 16K11843
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Periodontology
Research InstitutionNihon University

Principal Investigator

YAMAGUCHI Yoko  日本大学, 歯学部, 助教 (00239922)

Co-Investigator(Kenkyū-buntansha) 大島 光宏  奥羽大学, 薬学部, 教授 (30194145)
Research Collaborator HORIE Masafumi  
SAITO Akira  
KAPPART Kai  
MICKE Patrick  
ÖSTMAN Arne  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords初代培養 / 生体外歯周炎モデル / 歯周炎治療薬 / HGF / 3次元培養 / 初代培養細胞 / 初代培養上皮細胞 / 三次元培養 / コラーゲン分解 / 上皮細胞
Outline of Final Research Achievements

Therapeutic agent for periodontitis, in particular, a drug that exerts an effect by applying to gingival epithelium, was searched using periodontitis-causing fibroblasts-containing culture model that we have established. However, no candidate was found that could inhibit the degradation of collagen which connects teeth and bone only by acting on the epithelium.
Therefore, we have re-examined the periodontitis-causing fibroblasts, and found highly expression of hepatocyte growth factor (HGF) during collagen degradation. Using neutralizing antibody to inhibit HGF activity, it was found that the collagen degradation was inhibited in the model and furthermore, improved the clinical indices in monkeys that have naturally-occurred periodontitis.

Academic Significance and Societal Importance of the Research Achievements

これまで細菌が原因と勘違いされてきた歯周炎において、コラーゲン分解能力が極端に高い原因細胞とみられる細胞を取り出すとともに、三次元培養モデルを用いて原因候補となる遺伝子のひとつが肝細胞増殖因子(HGF)であることを突き止めた。このHGFの働きを止める中和抗体の効果をモデルで証明したのち、歯周炎を自然発症したサルの歯肉に注射したところ、その症状が改善した。これらのことから、本研究では世界で初めて歯周炎を抗体によって治療できる可能性を示唆することができた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (24 results)

All 2018 2017 2016 Other

All Int'l Joint Research (7 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results) Patent(Industrial Property Rights) (6 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Uppsala University(スウェーデン)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Charite(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Uppsala University(Sweden)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Charite(ドイツ)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Uppsala Univeristy(Sweden)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Charite(Germany)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Harry Perkins Institute of Medical Res(Australia)

    • Related Report
      2016 Research-status Report
  • [Journal Article] TBX4 is involved in the super-enhancer-driven transcriptional programs underlying features specific to lung fibroblasts.2018

    • Author(s)
      Horie M, Miyashita N, Mikami Y, Noguchi S, Yamauchi Y, Suzukawa M, Fukami T, Ohta K, Asano Y, Sato S, Yamaguchi Y, Ohshima M, Suzuki HI, Saito A, Nagase T.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol.

      Volume: 314 Issue: 1 Pages: L177-L191

    • DOI

      10.1152/ajplung.00193.2017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA profiling in gingival crevicular fluid of periodontitis-a pilot study2017

    • Author(s)
      Saito Akira、Horie Masafumi、Ejiri Kenichiro、Aoki Akira、Katagiri Sayaka、Maekawa Shogo、Suzuki Shinta、Kong Sophannary、Yamauchi Tsuneto、Yamaguchi Yoko、Izumi Yuichi、Ohshima Mitsuhiro
    • Journal Title

      FEBS Open Bio

      Volume: 7 Issue: 7 Pages: 981-994

    • DOI

      10.1002/2211-5463.12238

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated Genes in NSCLC2017

    • Author(s)
      Horie M, Kaczkowski B, Ohshima M, Matsuzaki H, Noguchi S, Mikami Y, Lizio M, Itoh M, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest ARR, Takai D, Yamaguchi Y, Micke P, Saito A, Nagase T.
    • Journal Title

      Mol Cancer Res.

      Volume: 15 Issue: 10 Pages: 1354-1365

    • DOI

      10.1158/1541-7786.mcr-17-0191

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.2016

    • Author(s)
      Horie M, Yamaguchi Y, Saito A, Nagase T, Lizio M, Itoh M, Kawaji H, Lassmann T, Carninci P, Forrest AR, Hayashizaki Y, Suzutani T, Kappert K, Micke P, Ohshima M.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1

    • DOI

      10.1038/srep33666

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] MicroRNA profiling in gingival crevicular fluid of periodontitis patients.2018

    • Author(s)
      Ohshima M, A. Saito, Horie M, Ejiri K, Aoki A, Katagiri S, Maekawa S, Suzuki S, Kong S, Yamauchi T, Yamaguchi Y, Izumi Y
    • Organizer
      EuroPerio9
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 糖尿病と歯周病:石川県羽咋郡市中野プロジェクト(その1)2018

    • Author(s)
      山内恒人,大島光宏,山口洋子,小西一典,衛藤雅昭,中野 茂
    • Organizer
      第71回東北地区歯科医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 屈折点による病変探索2018

    • Author(s)
      山口洋子, 山内恒人, 大島光宏, 小西一典, 中野 茂
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖尿病患者の洗口吐出液中HGF量とヘモグロビン量との関係について,2018

    • Author(s)
      大島光宏, 山内恒人, 山口洋子, 小西一典, 衛藤雅昭, 中野 茂
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖尿病患者と非糖尿病患者の洗口吐出液中HGFとヘモグロビンによる歯周炎診断の有用性について2018

    • Author(s)
      大島光宏,山内恒人,山口洋子,小西一典,衛藤雅昭,中野茂
    • Organizer
      第33回糖尿病合併症学会・第24回日本糖尿病眼科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 屈折点による病変探索2018

    • Author(s)
      山内恒人,山口洋子,大島光宏,小西一典,中野茂
    • Organizer
      第33回糖尿病合併症学会・第24回日本糖尿病眼科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Targeting hepatocyte growth factor as novel therapeutic approach for periodontitis2018

    • Author(s)
      Yamaguchi Y, Ohshima M
    • Organizer
      EuroPerio9
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] インプラント周囲炎の予防、及び/又は治療に使用する物質のスクリーニング方法、及びインプラント周囲炎の予防用、及び/又は治療用組成物2018

    • Inventor(s)
      山口洋子、大島光宏、深田一剛,巽一憲
    • Industrial Property Rights Holder
      日本大学、ロート製薬
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-202631
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 屈折点による病変探知2018

    • Inventor(s)
      山内恒人、大島光宏,山口洋子
    • Industrial Property Rights Holder
      日本大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-148587
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] miRNAをマーカーつする歯周炎検査キット、および検査方法2017

    • Inventor(s)
      大島光宏、山口洋子、齋藤朗、堀江真史、長瀬隆英、岩本久美
    • Industrial Property Rights Holder
      日本大学、東京大学、株式会社アイシーエレクトロニクス
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 歯周炎治療薬2017

    • Inventor(s)
      大島光宏、山口洋子、齋藤朗、堀江真史、長瀬隆英
    • Industrial Property Rights Holder
      日本大学、東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-101501
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 歯周炎治療薬および歯周炎治療組成物2017

    • Inventor(s)
      大島光宏、山口洋子
    • Industrial Property Rights Holder
      日本大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 歯周炎治療薬及び歯周炎治療用組成物2016

    • Inventor(s)
      山口洋子、大島光宏
    • Industrial Property Rights Holder
      日本大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-146593
    • Filing Date
      2016-07-26
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-22  

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