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Elucidation of mechanisms maintaining the homeostasis of quiescent periodontal stem cells demonstrated by tooth germ transplantation

Research Project

Project/Area Number 17K11953
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthodontics/Pediatric dentistry
Research InstitutionNiigata University

Principal Investigator

Nakakura-Ohshima Kuniko  新潟大学, 医歯学総合病院, 講師 (80213693)

Co-Investigator(Kenkyū-buntansha) 大島 勇人  新潟大学, 医歯学系, 教授 (70251824)
早崎 治明  新潟大学, 医歯学系, 教授 (60238095)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords歯胚移植 / 幹細胞 / 歯根膜 / GFP / TetOP-H2B-GFP / BrdU / TetOP-GFP
Outline of Final Research Achievements

In order to search the dynamics of periodontal ligament stem cells, we conducted a tooth germ transplantation experiment using mice. Since periodontal ligament stem cells cannot be labeled by the BrdU labeling method, stem cells/progenitor cells were labeled by administering doxycycline to the pregnant mother on 14.5 days of embryonic period. As a result, 25.0% of the transplanted tooth germs were found to have both odontoblast differentiation and root formation, and some specimens were erupted and occluded. Strongly GFP-positive cells, which are considered to be static stem cells, were maintained in the center of the pulp or the sub-odontoblastic layer, and differentiate into odontoblasts, whereas strongly GFP-positive cells were not found in the periodontal ligament. These results suggest that GFP-positive periodontal ligament stem cells maintained during tooth development are affected by allogenic tooth germ transplantation.

Academic Significance and Societal Importance of the Research Achievements

小児歯科臨床において、健常児における永久歯先天欠如や、小児白血病等腫瘍治療に伴う永久歯の歯根形成停止・歯胚欠如は大きな問題である。
これらの症例で、第三大臼歯等の歯胚を欠損部に移植できれば、小児期から骨を含めた形態的・機能的回復が可能となる。さらに、他家移植が可能となれば、成人の欠損補綴にも応用の可能性が拡大する。しかし、歯の生着および機能獲得には歯周組織の形成維持が重要であるものの、その生物学的エビデンスは乏しい。
本研究では、遺伝子改変マウスを用いた歯胚移植により、歯根膜幹細胞の動態およびその維持・分化機構を検索した。この成果は自家・他家歯胚移植の臨床応用に繋がる第一歩である。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (26 results)

All 2021 2020 2019 2018 2017

All Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 11 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results)

  • [Journal Article] The effects of reducing the root length by apicoectomy on dental pulp regeneration following tooth replantation in mice.2021

    • Author(s)
      Nakakura-Ohshima K, Quispe-Salcedo A, Sano H, Hayasaki H, Ohshima H
    • Journal Title

      Dent Traumatol

      Volume: 11 Issue: 5 Pages: 677-690

    • DOI

      10.1111/edt.12679

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of angiogenesis and pulpal healing in tooth replantation and allograft transplantation2021

    • Author(s)
      Lee Dong-Joon、Lee Seung-Jun、Lee Min-Jung、Kim Eun-Jung、Ohshima Hayato、Jung Han-Sung
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 26 Pages: 100945-100945

    • DOI

      10.1016/j.bbrep.2021.100945

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Responses of oral-microflora-exposed dental pulp to capping with a triple antibiotic paste or calcium hydroxide cement in mouse molars2020

    • Author(s)
      Quispe-Salcedo A, Sato T, Matsuyama J, Ida-Yonemochi H, Ohshima H
    • Journal Title

      Regen Ther

      Volume: 15 Pages: 216-225

    • DOI

      10.1016/j.reth.2020.10.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dentin Matrix Protein 1 Compensates for Lack of Osteopontin in Regulating Odontoblastlike Cell Differentiation after Tooth Injury in Mice2020

    • Author(s)
      Saito Kotaro、Nakatomi Mitsushiro、Ohshima Hayato
    • Journal Title

      Journal of Endodontics

      Volume: 46 Issue: 1 Pages: 89-96

    • DOI

      10.1016/j.joen.2019.10.002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunohistochemistry and gene expression of GLUT1, RUNX2 and MTOR in reparative dentinogenesis2020

    • Author(s)
      Takeuchi Ryosuke、Ohkura Naoto、Yoshiba Kunihiko、Tohma Aiko、Yoshiba Nagako、Edanami Naoki、Shirakashi Mari、Belal Razi Saifullah Ibn、Ohshima Hayato、Noiri Yuichiro
    • Journal Title

      Oral Diseases

      Volume: 26 Issue: 2 Pages: 341-349

    • DOI

      10.1111/odi.13230

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucose Transporter 2 and 4 Are Involved in Glucose Supply during Pulpal Wound Healing after Pulpotomy with Mineral Trioxide Aggregate in Rat Molars2020

    • Author(s)
      Tohma Aiko、Ohkura Naoto、Yoshiba Kunihiko、Takeuchi Ryosuke、Yoshiba Nagako、Edanami Naoki、Shirakashi Mari、Ibn Belal Razi Saifullah、Ohshima Hayato、Noiri Yuichiro
    • Journal Title

      Journal of Endodontics

      Volume: 46 Issue: 1 Pages: 81-88

    • DOI

      10.1016/j.joen.2019.10.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduced enamel epithelium-derived cell niche in the junctional epithelium are maintained for a long time in mice2019

    • Author(s)
      Soda M, Saito K, Ida-Yonemochi H, Nakakura-Ohshima K, Kenmotsu S, Ohshima H
    • Journal Title

      J Periodontol

      Volume: Sep 9 Issue: 6 Pages: 819-827

    • DOI

      10.1002/jper.19-0269

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Repeated human deciduous tooth-derived dental pulp cell reprogramming factor transfection yields multipotent intermediate cells with enhanced iPS cell formation capability2019

    • Author(s)
      Soda Miki、Saitoh Issei、Murakami Tomoya、Inada Emi、Iwase Yoko、Noguchi Hirofumi、Shibasaki Shinji、Kurosawa Mie、Sawami Tadashi、Terunuma Miho、Kubota Naoko、Terao Yutaka、Ohshima Hayato、Hayasaki Haruaki、Sato Masahiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1490-1490

    • DOI

      10.1038/s41598-018-37291-2

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The putative role of insulin-like growth factor (IGF)-binding protein 5 independent of IGF in the maintenance of pulpal homeostasis in mice.2019

    • Author(s)
      Saito K, Ohshima H
    • Journal Title

      Regen Ther

      Volume: 11 Pages: 217-224

    • DOI

      10.1016/j.reth.2019.08.001

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Donor-host tissue interaction in the allogenic transplanted tooth germ with special reference to periodontal tissue2018

    • Author(s)
      Nakaki T, Nakakura-Ohshima K, Nakagawa E, Ishikawa Y, Saito K, Ida-Yonemochi H, Ohshima H
    • Journal Title

      Journal of Oral Biosciences

      Volume: 60 Issue: 1 Pages: 21-30

    • DOI

      10.1016/j.job.2018.02.002

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differentiation capacity and maintenance of dental pulp stem/progenitor cells in the process of pulpal healing following tooth injuries.2017

    • Author(s)
      Saito K, Ohshima H
    • Journal Title

      J Oral Biosci

      Volume: 59(2) Issue: 2 Pages: 63-70

    • DOI

      10.1016/j.job.2017.03.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Isolation and characterization of lymphoid enhancer factor-1-positive deciduous dental pulp stem-like cells after transfection with a piggyBac vector containing LEF1 promoter-driven selection markers.2017

    • Author(s)
      Murakami T, Saitoh I, Sato M, Inada E, Soda M, Oda M, Domon H, Iwase Y, Sawami T, Matsueda K, Terao Y, Ohshima H, Noguchi H, Hayasaki H
    • Journal Title

      Archives of Oral Biology

      Volume: 81 Pages: 110-120

    • DOI

      10.1016/j.archoralbio.2017.04.033

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Osteopontin and root development stage are essential for pulpal healing following tooth replantation.2021

    • Author(s)
      Suzuki Kiyoko,真喜志佐奈子,中富満城,斎藤浩太郎,依田浩子, 大島勇人
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Role of osteopontin in the process of pulpal healing following tooth replantation in mice.2020

    • Author(s)
      Suzuki K,Makishi S,Nakatomi M,Saito K,Ida-Yonemochi H,Ohshima H
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マウス歯髄組織の発生・再生治癒過程におけるコンドロイチン硫酸の機能発現.2020

    • Author(s)
      依田 浩子,大島 勇人
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The function of IGFBP3 and IGFBP5 during tooth development and pulpal healing after tooth injury.2019

    • Author(s)
      Ohshima H, Aizawa C, Saito K
    • Organizer
      13th Tooth Morphogenesis & Differentiation (TMD) Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dental epithelial stem cells are maintained under condition of low oxygen level.2019

    • Author(s)
      Otsu K, Ikezaki S, Ohshima H, Harada H
    • Organizer
      13th Tooth Morphogenesis & Differentiation (TMD) Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 歯髄恒常性維持に関わるinsulin-like growth factor (IGF) binding protein 5のIGF非依存的役割2019

    • Author(s)
      大島勇人,斎藤浩太郎
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 歯根切除が歯の再植・移植後の歯髄歯根膜治癒過程に及ぼす影響について2019

    • Author(s)
      大島邦子,早崎治明
    • Organizer
      第57回日本小児歯科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] The role of subodontoblastic layer for pulpal healing after tooth injuries.2018

    • Author(s)
      Ohshima H, Saito K, Nakatomi M, Ida-Yonemochi H
    • Organizer
      6th Tripartite Conference on Tooth and Bone in Development & Regeneration
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Pulpal healing mechanism after exogenous tooth injuries and prospects for regenerative medicine in dentistry.2018

    • Author(s)
      Ohshima H
    • Organizer
      5th TERMIS World, Symposia
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] マウス歯肉接合上皮細胞の由来と動態について2018

    • Author(s)
      斎藤浩太郎,依田浩子,大島邦子,大島勇人
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 外的侵襲後の歯髄修復メカニズムと再生医学への展開2017

    • Author(s)
      大島勇人
    • Organizer
      第17回日本外傷歯学会総会・学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 歯の外的侵襲後の歯髄修復機構と歯髄幹細胞の特性2017

    • Author(s)
      大島勇人
    • Organizer
      第59回歯科基礎医学会学術大会日韓シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 歯の発生・創傷治癒過程における歯髄恒常性維持に関わるIGF binding protein 5の役割2017

    • Author(s)
      斎藤浩太郎,大島勇人
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 他家歯胚移植におけるドナー・ホスト相互作用:歯周組織に着目して2017

    • Author(s)
      中木哲朗,大島邦子,石川裕子,斎藤浩太郎,依田浩子,大島勇人
    • Organizer
      平成29年度新潟歯学会第2回例会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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