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regeneration of teeth by targeted therapy with cebpb as the target molecule

Research Project

Project/Area Number 17K11832
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionKyoto University

Principal Investigator

takahashi katsu  京都大学, 医学研究科, 准教授 (90314202)

Co-Investigator(Kenkyū-buntansha) 別所 和久  京都大学, 医学研究科, 教授 (90229138)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords歯の再生 / エナメル上皮幹細胞 / CEBP/β / 分子標的治療 / Cebpβ / Runx2 / siRNA / mHAT9d細胞 / 体性幹細胞 / 再生医学
Outline of Final Research Achievements

We have been working on tooth regeneration research by molecular targeted therapy focusing on the molecular mechanism of tooth number control that can actually be applied clinically. The phenotype of double gene-modified mice of Cebpβ and Runx2 was analyzed. It was revealed in vivo that Cebpβ is involved in maintaining stemness of enamel epithelial stem cells and that epithelial-mesenchymal transition is involved in supernumerary tooth formation. Similar results were obtained in an in vitro experimental system using the enamel epithelial stem cell-like mHAT9d cells. Furthermore, the involvement of odontogenic epithelial stem cells in excess tooth formation in humans was examined, and it was suggested that odontogenic epithelial stem cells may be involved in excess tooth formation when the third ridge is not the cause.

Academic Significance and Societal Importance of the Research Achievements

歯の再生に関する研究は、これまで組織工学的な手法を用いた方法が数多く報告されてきたが、コストや安全性等の問題で、臨床応用まで至っていない。そのため、われわれは実際に臨床展開が可能な歯数制御の分子メカニズムに着目した分子標的治療による歯の再生研究に取り組んだ。将来的には国内に3000万人以上とされる欠損歯患者を対象にエナメル上皮幹細胞にCEBP/βの分子標的薬を局所投与することにより歯を再生する治療法を確立する。本研究が実用化されれば、歯科医療の抜本的改革に貢献できることに大きな意義があると考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (21 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (8 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (7 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] University of British Coiumbia(カナダ)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Charles Sturt University(オーストラリア)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Univ British Columbia(Canada)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Charles Sturt Univ(Australia)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Third Dentition Is the Main Cause of Premolar Supernumerary Tooth Formation2019

    • Author(s)
      Kiso H.、Takahashi K.、Mishima S.、Murashima-Suginami A.、Kakeno A.、Yamazaki T.、Asai K.、Tokita Y.、Uozumi R.、Sugai M.、Harada H.、Huang B.、MacDougall M.、Bessho K.
    • Journal Title

      Journal of Dental Research

      Volume: 98 Issue: 9 Pages: 968-974

    • DOI

      10.1177/0022034519858282

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Loss of Stemness, EMT, and Supernumerary Tooth Formation in Cebpb-/-Runx2+/- Murine Incisors.2018

    • Author(s)
      Saito K, Takahashi K, Huang B, Asahara M, Kiso H, Togo Y, Tsukamoto H, Mishima S, Nagata M, Iida M, Tokita Y, Asai M, Shimizu A, Komori T, Harada H, MacDougall M, Sugai M, Bessho K.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 5169-5169

    • DOI

      10.1038/s41598-018-23515-y

    • NAID

      120006545187

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An anti-peptide monoclonal antibody recognizing the tobacco etch virus protease-cleavage sequence and its application to a tandem tagging system2018

    • Author(s)
      Tabata Sanae、Kitago Yu、Fujii Yuki、Mihara Emiko、Tamura-Kawakami Keiko、Norioka Naoko、Takahashi Katsu、Kaneko Mika K.、Kato Yukinari、Takagi Junichi
    • Journal Title

      Protein Expr Purif.

      Volume: 147 Pages: 94-99

    • DOI

      10.1016/j.pep.2018.03.004

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Maxillary Hypoplasia With Congenital Oligodontia Treated by Maxillary Distraction Osteogenesis2018

    • Author(s)
      Mishima Sayaka、Yamaguchi Takako、Watanabe Takuma、Komatani Toru、Nakao Kazumasa、Takahashi Katsu、Bessho Kazuhisa
    • Journal Title

      Journal of Craniofacial Surgery

      Volume: 29 Issue: 4 Pages: e411-e414

    • DOI

      10.1097/scs.0000000000004414

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Gender differences in morphological and functional outcomes after mandibular setback surgery2018

    • Author(s)
      Dahy Khaled、Takahashi Katsu、Saito Kazuyuki、Kiso Honoka、Rezk Ibrahim、Oga Toru、Uozumi Ryuji、Chin Kazuo、Bessho Kazuhisa
    • Journal Title

      Journal of Cranio-Maxillofacial Surgery

      Volume: 46 Issue: 6 Pages: 887-892

    • DOI

      10.1016/j.jcms.2018.04.006

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Direct evidence for the age-dependent demise of GNAS -mutated cells in oral fibrous dysplasia2018

    • Author(s)
      Isobe Yu、Takahashi Katsu、Kiso Honoka、Nakao Kazumasa、Ikeno Masayuki、Koyama Noriaki、Sugai Manabu、Shimizu Akira、Haga Hironori、Bessho Kazuhisa
    • Journal Title

      Archives of Oral Biology

      Volume: 93 Pages: 133-140

    • DOI

      10.1016/j.archoralbio.2018.05.018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel RUNX2/CBFA1 mutation at the runt domain in a Japanese patient with cleidocranial dysplasia2017

    • Author(s)
      Gotoh, H., J. Machida, J., Shibata, A., Tatematsu, T., Miyachi, H., Takahashi, K., Nakayama, A., Y. Higashi, Y., T. Nagao, T., Shimozato, K., Tokita, Y.
    • Journal Title

      J Oral Maxillofac Surg Med Path

      Volume: 29 Issue: 3 Pages: 222-224

    • DOI

      10.1016/j.ajoms.2016.10.009

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] WNT10A variants isolated from Japanese patients with congenital tooth agenesis2017

    • Author(s)
      Machida J., Goto H., Tatematsu T., Shibata A., Miyachi H., Takahashi K., Izumi H., Nakayama A., Shimozato K., Tokita Y.
    • Journal Title

      Hum Genome Var

      Volume: 9 Issue: 1 Pages: 17047-17047

    • DOI

      10.1038/hgv.2017.47

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 希少疾患先天性無歯症治療薬の開発研究-Wntシグナル&BMPシグナルに関連する難治性疾患治療への展開-2020

    • Author(s)
      高橋 克
    • Organizer
      難治性疾患実用化研究事業 免疫アレルギー疾患実用化研究事業 2019年度合同成果報告会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 歯数制御による歯の再生治療薬の開発2019

    • Author(s)
      高橋克、喜早ほのか、三島清香、杉並亜希子、時田義人、田畑泰彦、菅井学、別所和久
    • Organizer
      第40回 日本炎症・再生医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 分子標的治療による欠損歯の再生2017

    • Author(s)
      高橋克、喜早ほのか、斎藤和幸、東郷由弥子、塚本容子、三島清香、杉並
    • Organizer
      第16回 日本再生医療学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] マウス切歯体性幹細胞を用いた歯の再生モデル2017

    • Author(s)
      斎藤和幸、高橋克、喜早ほのか、東郷由弥子、塚本容子、三島清香、Dahy Ahamed Khared Gamel、Marziyer Aghazadeh、菅井学、永田昌毅、原田英光、別所和久
    • Organizer
      第16回 日本再生医療学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 歯数制御による歯の再生治療薬の開発2017

    • Author(s)
      高橋克、喜早ほのか、斎藤和幸、杉並亜希子、三島清香、田畑泰彦、別所和久
    • Organizer
      第33回 日本DDS学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒト非症候群性過剰歯の発生由来に関する免疫組織学的検討2017

    • Author(s)
      喜早ほのか、高橋克、源健文、西村隆克、斎藤和幸、浅井啓太、三島清香、別所和久
    • Organizer
      第62回 日本口腔外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 上顎前歯部における過剰歯の存在割合と存在部位に関する検討2017

    • Author(s)
      西村隆克、三島清香、懸野安澄、斎藤和幸、喜早ほのか、浅井啓太、高橋克、三島清香、別所和久
    • Organizer
      第62回 日本口腔外科学会総会
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] USAG-1を標的とするRNA分子を含む歯の再生治療薬2020

    • Inventor(s)
      高橋克、菅井学、時田義人、別所和久、田畑泰彦
    • Industrial Property Rights Holder
      高橋克、菅井学、時田義人、別所和久、田畑泰彦
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-028547
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] USAG-1を標的分子とした歯数制御による歯の再生治療薬(中和抗体)2019

    • Inventor(s)
      高橋克、菅井学、時田義人、高木淳一、三原恵美子
    • Industrial Property Rights Holder
      高橋克、菅井学、時田義人、高木淳一、三原恵美子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-130153
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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