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The tooth germ is formed utilizing induction of Epithelial to Mesenchymal Transition (EMT) from epithelium

Research Project

Project/Area Number 18H03009
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57070:Developmental dentistry-related
Research InstitutionTohoku University

Principal Investigator

齋藤 幹  東北大学, 大学病院, 講師 (40380852)

Co-Investigator(Kenkyū-buntansha) 福本 敏  九州大学, 歯学研究院, 教授 (30264253)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Granted (Fiscal Year 2022)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2022: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2021: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords歯原性上皮 / エナメル芽細胞 / EMT / 骨代謝
Outline of Annual Research Achievements

以前の研究でSox21が歯のエナメル質形成や、上皮間葉転換(EMT)に重要であることを報告したが、骨形成にも異常が見られる事が示唆された。、しかしながら硬組織におけるEMT研究はほとんど行われていないのが現状である。そこで、Sox21の発現を網羅的に解析したところ、骨髄で発現する事が明らかとなった。そこで、骨髄細胞において、Sox21の発現を更に検討したところ、T細胞やB細胞で発現が認められた。この結果から石灰化を誘導する分子が、免疫系にも関与している可能性が示唆された。EMTを起こす環境として、癌化が挙げられる。通常、癌化した細胞は免疫によって排除されるが、この免疫チェックポイントをすり抜けることにより、癌細胞が増殖する。Sox21が癌化に関与していると言う報告もあり、Sox21は石灰化やEMTだけで無く、免疫にも関与している可能性が示された。歯胚を原発とする腫瘍として、エナメル上皮腫が挙げられるが、その発生頻度は低い。今回の結果は、歯を形成する分子が癌化を抑制し、免疫や石灰化を亢進させている可能性が考えられた。そこで、歯の石灰化に関与する分子をスクリーニングしたところ、腫瘍マーカーとして知られる分子が、成熟エナメル芽細胞で複数発現していることを突き止めた。その内、1つの分子の発現をエナメル芽細胞で抑制させたところ、Sox21の発現が上昇し、間葉系マーカーの発現が減少した。この様に石灰化とEMTに関連する分子はSox21以外にも存在することが明らかとなった。

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

マウスの繁殖が進んでおらず、充分なOKマウスが手に入らない状況である。

Strategy for Future Research Activity

前年度の研究の結果から、歯原性上皮のEMTに関与する分子として、Sox21以外にも複数存在することが明らかとなった。さらにその経路は免疫チェックポイントにも関与している可能性が示された。そこで、その他分子についても、エナメル芽細胞における石灰化やEMTとの関連について検討を行っていく。

Report

(4 results)
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(20 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (16 results) (of which Int'l Joint Research: 13 results,  Peer Reviewed: 16 results,  Open Access: 14 results) Presentation (2 results) Remarks (2 results)

  • [Journal Article] Integration of Single-Cell RNA- and CAGE-seq Reveals Tooth-Enriched Genes2022

    • Author(s)
      Chiba Y.、Yoshizaki K.、Tian T.、Miyazaki K.、Martin D.、Saito K.、Yamada A.、Fukumoto S.、Genomics and Computational Biology Core
    • Journal Title

      Journal of Dental Research

      Volume: - Pages: 002203452110497-002203452110497

    • DOI

      10.1177/00220345211049785

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The tooth-specific basic-helix-loop-helix factor AmeloD promotes differentiation of ameloblasts2022

    • Author(s)
      Jia L, Chiba Y, Saito K, Yoshizaki K, Tian T, Han X, Mizuta K, Chiba M, Wang X, Al Thamin S, Yamada A, Fukumoto S.
    • Journal Title

      Journal of Cellular Physiology

      Volume: 237(2) Pages: 1597-1606

    • DOI

      10.1002/jcp.30639

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] von Willebrand factor D and EGF domains regulate ameloblast differentiation and enamel formation.2022

    • Author(s)
      Iwata K, Kawarabayashi K, Yoshizaki K, Tian T, Saito K, Sugimoto A, Kurogoushi R, Yamada A, Yamamoto A, Kudo Y, Ishimaru N, Fukumoto S, Iwamoto T.
    • Journal Title

      Journal of Cellular Physiology

      Volume: 237 Pages: 1964-1979

    • DOI

      10.1002/jcp.30667

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptional regulation of the basic helix-loop-helix factor AmeloD during tooth development2021

    • Author(s)
      Al Thamin S, Chiba Y, Yoshizaki K, Tian T, Jia L, Wang X, Saito K, Li J, Yamada A, Fukumoto S.
    • Journal Title

      Journal of Cellular Physiology

      Volume: 236(11) Pages: 7533-7543

    • DOI

      10.1002/jcp.30389

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Connexin 43-mediated gap junction communication regulates ameloblast differentiation via ERK1/2 phosphorylation2021

    • Author(s)
      Yamada A, Yoshizaki K, Ishikawa M, Saito K, Chiba Y, Fukumoto E, Hoshikawa S, Chiba M, Nakamura T, Iwamoto T, Fukumoto S.
    • Journal Title

      Frontiers in Physiology

      Volume: 12 Pages: 748574-748574

    • DOI

      10.3389/fphys.2021.748574

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-Cell RNA-Sequencing From Mouse Incisor Reveals Dental Epithelial Cell-Type Specific Genes2021

    • Author(s)
      Chiba Y, Saito K, Martin D, Boger ET, Rhodes C, Yoshizaki K, Nakamura T, Yamada A, Morell RJ, Yamada Y, Fukumoto S.
    • Journal Title

      Front Dev Cell Biol

      Volume: 8 Pages: 841-841

    • DOI

      10.3389/fcell.2020.00841

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ2020

    • Author(s)
      Saito K, Michon F, Yamada A, Inuzuka H, Yamaguchi S, Fukumoto E, Yoshizaki K, Nakamura T, Arakaki M, Chiba Y, Ishikawa M, Okano H, Thesleff I, Fukumoto S.
    • Journal Title

      iSCIENCE

      Volume: 23 Pages: 101329-101329

    • DOI

      10.1016/j.isci.2020.101329

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphorylation‐dependent osterix degradation negatively regulates osteoblast differentiation2020

    • Author(s)
      Hoshikawa Seira、Shimizu Kouhei、Watahiki Asami、Chiba Mitsuki、Saito Kan、Wei Wenyi、Fukumoto Satoshi、Inuzuka Hiroyuki
    • Journal Title

      FASEB Journal

      Volume: 34 Pages: 14930-14945

    • DOI

      10.1096/fj.202001340r

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] G protein coupled receptor Gpr115 (Adgrf4) is required for enamel mineralization mediated by ameloblasts2020

    • Author(s)
      Chiba Yuta、Yoshizaki Keigo、Saito Kan、Ikeuchi Tomoko、Iwamoto Tsutomu、Rhodes Craig、Nakamura Takashi、de Vega Susana、Morell Robert J.、Boger Erich T.、Martin Daniel、Hino Ryoko、Inuzuka Hiroyuki、Bleck Christopher K.E.、Yamada Aya、Yamada Yoshihiko、Fukumoto Satoshi
    • Journal Title

      J Biol Chem

      Volume: 295 Pages: 15328-15341

    • DOI

      10.1074/jbc.ra120.014281

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Melnick-Needles syndrome associated molecule, Filamin-A regulates dental epithelial cell migration and root formation2020

    • Author(s)
      Hino Ryoko、Yamada Aya、Chiba Yuta、Yoshizaki Keigo、Fukumoto Emiko、Iwamoto Tsutomu、Maruya Yuriko、Otsu Keishi、Harada Hidemistu、Saito Kan、Fukumoto Satoshi
    • Journal Title

      Pediatric Dental Journal

      Volume: 30 Pages: 208-214

    • DOI

      10.1016/j.pdj.2020.09.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression Patterns of Claudin Family Members During Tooth Development and the Role of Claudin-10 (Cldn10) in Cytodifferentiation of Stratum Intermedium2020

    • Author(s)
      Wang Xin、Chiba Yuta、Jia Lingling、Yoshizaki Keigo、Saito Kan、Yamada Aya、Qin Man、Fukumoto Satoshi
    • Journal Title

      Front Dev Cell Biol

      Volume: 8 Pages: 595593-595593

    • DOI

      10.3389/fcell.2020.595593

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification and function analysis of ameloblast differentiation-related molecules using mouse incisors2020

    • Author(s)
      Saito Kan、Chiba Yuta、Yamada Aya、Fukumoto Satoshi
    • Journal Title

      Pediatric Dental Journal

      Volume: 30 Pages: 129-138

    • DOI

      10.1016/j.pdj.2020.08.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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

      Frontiers in Cell and Developmental Biology

      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 AmeloD stimulates epithelial cell motility essential for tooth morphology.2019

    • Author(s)
      Chiba Y, He B, Yoshizaki K, Rhodes C, Ishijima M, Bleck CKE, Stempinski E, Chu EY, Nakamura T, Iwamoto T, de Vega S, Saito K, Fukumoto S, Yamada Y
    • Journal Title

      J Biol Chem.

      Volume: 294(10) Pages: 3406-3418

    • DOI

      10.1074/jbc.ra118.005298

    • NAID

      120007168786

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pannexin 3 ER Ca2+ channel gating is regulated by phosphorylation at the Serine 68 residue in osteoblast differentiation2019

    • Author(s)
      Ishikawa Masaki、Williams Geneva、Forcinito Patricia、Ishikawa Momoko、Petrie Ryan J.、Saito Kan、Fukumoto Satoshi、Yamada Yoshihiko
    • Journal Title

      Scientific reports

      Volume: 9 Pages: 18759-18759

    • DOI

      10.1038/s41598-019-55371-9

    • 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

      The Journal of biological chemistry

      Volume: 293 Pages: 38-14572

    • DOI

      10.1074/jbc.ra118.003373

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 転写因子AmeloDが制御する新規エナメル質形成分子機序の解明2021

    • Author(s)
      賈 玲玲、千葉雄太、吉崎恵悟、齋藤 幹、福本 敏
    • Organizer
      第59回日本小児歯科学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] シングルセルRNAシークエンスを用いた歯の発生に関わる全細胞の網羅的遺伝子解析2020

    • Author(s)
      千葉雄太、齋藤 幹、日野綾子、新垣真紀子、小山田優、丸谷由里子、山田 亜矢、福本 敏
    • Organizer
      日本小児歯科学会大会
    • Related Report
      2020 Annual Research Report
  • [Remarks] 歯をつくる細胞から毛髪細胞へ変化させる分子を同定

    • URL

      https://www.tohoku.ac.jp/japanese/2020/07/press20200728-03-Sox.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 歯の石灰化を制御する新規の受容体を同定

    • URL

      https://www.tohoku.ac.jp/japanese/2020/11/press20201106-01-enamel.html

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-12-28  

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