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Analysis of growth factor - intercellular communication during dental epithelial and mesenchymal cell differentiation.

Research Project

Project/Area Number 16H05548
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthodontics/Pediatric dentistry
Research InstitutionTohoku University

Principal Investigator

YAMADA AYA  東北大学, 歯学研究科, 准教授 (40295085)

Co-Investigator(Kenkyū-buntansha) 犬塚 博之  東北大学, 歯学研究科, 准教授 (20335863)
福本 敏  九州大学, 歯学研究院, 教授 (30264253)
阪井 丘芳  大阪大学, 歯学研究科, 教授 (90379082)
保住 建太郎  東京薬科大学, 薬学部, 講師 (10453804)
石河 真幸  東北大学, 大学病院, 助教 (60432936)
福島 秀文  東北大学, 歯学研究科, 准教授 (70412624)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywords再生医療 / 細胞間結合 / 増殖因子
Outline of Final Research Achievements

Intercellular junctions are thought to be important for signal transduction between cells and maintaining the barrier function of the epithelium. We focused on gap junctions among intercellular junctions, and examined the role of connexin 43, which is highly expressed during tooth development.
Connexin 43 is involved in the transport of small molecules such as calcium and IP3 between cells. In the deficiency of Connexin43, extracellular calcium transport is reduced, because of reduction of growth factors signaling such as TGF-beta1. And it is strictly regulating intracellular calcium levels. We have found new findings that determine the level of intracellular signal transduction via gap junction.

Academic Significance and Societal Importance of the Research Achievements

歯や唾液腺の器官形成において細胞間結合の役割を解明する事で、これまでその発症原因が不明であった眼歯指異形成症の病態解明に大きく貢献することができた。また細胞間結合は人為的調整が可能であることから、歯および唾液腺の器官再生技術の開発において、器官形成の促進化技術に応用可能な知見となる。これらは口腔組織のみならず肺、腎臓、肝臓等の全身の臓器形成にも応用可能な技術であり、さらにiPS細胞からは関連細胞の誘導や人工歯胚の形成にも成功している。また細胞内のカルシウムレベルの新たな調整機構解明は、ほぼ全ての細胞内シグナル伝達機構に関与しており、すべての生物学の基盤となる知見として役立つことが期待される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (10 results)

All 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) (of which Invited: 1 results)

  • [Int'l Joint Research] 米国国立衛生研究所(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] 北京大学(中国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Regulation of miR-1-Mediated Connexin 43 Expression and Cell Proliferation in Dental Epithelial Cells.2020

    • Author(s)
      Nakamura T, Iwamoto T, Nakamura HM, Shindo Y, Saito K, Yamada A, Yamada Y, Fukumoto S, Nakamura T.
    • Journal Title

      Front Cell Dev Biol.

      Volume: 17(8) Pages: 156-156

    • DOI

      10.3389/fcell.2020.00156

    • NAID

      120006869515

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The transcription factor NKX2-3 mediates p21 expression and ectodysplasin-A signaling in the enamel knot for cusp formation in tooth development2018

    • Author(s)
      Han Xue、Yoshizaki Keigo、Miyazaki Kanako、Arai Chieko、Funada Keita、Yuta Tomomi、Tian Tian、Chiba Yuta、Saito Kan、Iwamoto Tsutomu、Yamada Aya、Takahashi Ichiro、Fukumoto Satoshi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 293 Issue: 38 Pages: 14572-14584

    • DOI

      10.1074/jbc.ra118.003373

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NOTCH2 Hajdu-Cheney Mutations Escape SCFFBW7-Dependent Proteolysis to Promote Osteoporosis.2017

    • Author(s)
      Fukushima H, Shimizu K, Watahiki A, Hoshikawa S, Kosho T, Oba D, Sakano S, Arakaki M
    • Journal Title

      Mol Cell

      Volume: Nov 16;68(4) Issue: 4 Pages: 645-658

    • DOI

      10.1016/j.molcel.2017.10.018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nephronectin plays critical roles in Sox2 expression and proliferation in dental epithelial stem cells via EGF-like repeat domains.2017

    • Author(s)
      Arai C, Yoshizaki K, Miyazaki K, Saito K, Yamada A, Han X, Funada K, Fukumoto E, Haruyama N, Iwamoto T, Takahashi I, Fukumoto S.
    • Journal Title

      Sci Rep.

      Volume: 27 Issue: 1 Pages: 45181-45181

    • DOI

      10.1038/srep45181

    • NAID

      120006534986

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The SCFβ-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis.2017

    • Author(s)
      Shimizu K, Fukushima H, Ogura K, Lien EC, Nihira NT, Zhang J, North BJ, Guo A, Nagashima K, Nakagawa T, Hoshikawa S, Watahiki A, Okabe K, Yamada A, Toker A, Asara JM, Fukumoto S, Nakayama KI, Nakayama K, Inuzuka H, Wei W.
    • Journal Title

      Sci Signal. doi: 10.1126/scisignal.aah4117.

      Volume: 10 Issue: 460 Pages: 1-15

    • DOI

      10.1126/scisignal.aah4117

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN couplex localization and promotes renal cancer progression2016

    • Author(s)
      Nagashima, K., Fukushima, H., Shimizu, K., Hidaka, M., Hasumi, H., Ikebe, T., Fukumoto, S., Okabe, K., Inuzuka, H.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 6 Pages: 9947-9960

    • DOI

      10.18632/oncotarget.14221

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 内エナメル上皮の新規マーカーAmeloDの転写制御機構解明2019

    • Author(s)
      Shahad al Thamin、千葉雄太、吉崎恵悟、Ling Ling Jia、山田亜矢、齋藤幹、福本敏
    • Organizer
      第57回日本小児歯科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 口腔上皮器官形成における細胞間結合の機能とその制御2017

    • Author(s)
      山田亜矢
    • Organizer
      第55回日本小児歯科学会大会(学術賞受賞講演)
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2016-04-21   Modified: 2022-01-28  

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