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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

Saito Kan  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 Completed (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硬組織形成 / EMT / 歯原性上皮 / エナメル芽細胞 / 骨代謝
Outline of Final Research Achievements

Teeth are formed by the interrelationship between epithelial and mesenchymal cells. However, if epithelial-mesenchymal transition (EMT) which induces mesenchymal cells from epithelial cells is used, organ will generate from single epithelial cell. In our previous study, we found that Sox21 KO mice induce EMT. Therefore, in this study, we analyze the mechanism of EMT in hard tissue formation.
At first, Sox21 was expressed in T and B cells.
Therefore, when macrophages and lymphocytes with suppressed expression of Sox21 were co-cultured, osteoclast differentiation was enhanced. This indicates that while Sox21 deficiency causes EMT, it also promotes osteoclast differentiation and causes osteogenesis imperfecta-like symptoms.

Academic Significance and Societal Importance of the Research Achievements

本研究ではSox21を欠損させることにより、骨形成が抑制された。そのため、Sox21が骨粗鬆症の改善に貢献する可能性がある。また,Sox21はヒト13番染色体に位置する。13q欠失症候群のうち、Sox21が存在する13q32部が欠損すると重篤化する事が知られており、知的能力障害、成長遅延や癌化リスクの上昇が報告されている。そのため、本研究結果は13q欠失症候群における病態解明にも寄与すると考えられる。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (22 results)

All 2023 2022 2021 2020 2019 2018 Other

All Journal Article (18 results) (of which Int'l Joint Research: 14 results,  Peer Reviewed: 18 results,  Open Access: 16 results) Presentation (2 results) Remarks (2 results)

  • [Journal Article] Deficiency of G protein‐coupled receptor <i>Gpr111/Adgrf2</i> causes enamel hypomineralization in mice by alteration of the expression of kallikrein‐related peptidase 4 ( <i>Klk4</i> ) during <scp>pH</scp> cycling process2023

    • Author(s)
      Chiba Yuta、Yoshizaki Keigo、Sato Hiroshi、Ikeuchi Tomoko、Rhodes Craig、Chiba Mitsuki、Saito Kan、Nakamura Takashi、Iwamoto Tsutomu、Yamada Aya、Yamada Yoshihiko、Fukumoto Satoshi
    • Journal Title

      The FASEB Journal

      Volume: 37 Issue: 4

    • DOI

      10.1096/fj.202202053r

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GSK3beta inhibitor-induced dental mesenchymal stem cells regulate ameloblast differentiation2022

    • Author(s)
      Yamada Aya、Yoshizaki Keigo、Saito Kan、Ishikawa Masaki、Chiba Yuta、Hoshikawa Seira、Chiba Mitsuki、Hino Ryoko、Maruya Yuriko、Sato Hiroshi、Masuda Keiji、Yamaza Haruyoshi、Nakamura Takashi、Iwamoto Tsutomu、Fukumoto Satoshi
    • Journal Title

      Journal of Oral Biosciences

      Volume: 64 Issue: 4 Pages: 400-409

    • DOI

      10.1016/j.job.2022.10.002

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [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) Issue: 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

      J Cell Physiol.

      Volume: 237 Issue: 3 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) Issue: 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] Integration of Single-Cell RNA- and CAGE-seq Reveals Tooth-Enriched Genes2021

    • 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: - Issue: 5 Pages: 002203452110497-002203452110497

    • DOI

      10.1177/00220345211049785

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / 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 Issue: 7 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] Single-Cell RNA-Sequencing From Mouse Incisor Reveals Dental Epithelial Cell-Type Specific Genes2020

    • 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 Cell Dev 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] 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

      The FASEB Journal

      Volume: 34 Issue: 11 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

      Journal of Biological Chemistry

      Volume: 295 Issue: 45 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 Issue: 3 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

      Frontiers in Cell and Developmental Biology

      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 Issue: 3 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

      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 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) Issue: 10 Pages: 3406-3418

    • DOI

      10.1074/jbc.ra118.005298

    • 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 Issue: 1 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

      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
  • [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

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Published: 2018-04-23   Modified: 2024-01-30  

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