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Elucidation of the pathophysiology of cleidocranial dysplasia using disease-specific iPS cells

Research Project

Project/Area Number 16K20428
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional basic dentistry
Research InstitutionTokyo Dental College

Principal Investigator

Saito Akiko  東京歯科大学, 歯学部, 助教 (90722835)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords疾患iPS細胞 / 骨芽細胞分化 / 鎖骨頭蓋骨異形成症 / RUNX2 / 疾患特異的iPS細胞 / iPS細胞
Outline of Final Research Achievements

We established cleidocranial dysplasia (CCD)-derived iPS cells (CCD-iPSCs) and also established Revertant-iPSCs in which RUNX2 mutation of CCD-iPSCs was corrected by CRISPR / Cas method. These iPSCs had pluripotency. In osteogenic induction analysis, expression of osteoblast differentiation markers such as ALP, OSX, OCN, and DLX5 was increased only in Revertant-iPSCs. In the rat calvarial bone defects transplantation experiment, the bone closure delay was observed in the CCD transplant group, and both bone volume and bone mineral content were lower than Revertant transplant group. From the above results, it was confirmed that the established CCD-iPSCs exhibited bone mineralization disorder accompanying osteoblast differentiation abnormality.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia showed corrected osteoblastic differentiation both in vitro and in vivo.2018

    • Author(s)
      Ooki A, Nakamura T, Onodera S, Hayashi K, Hasegawa D, Kato H, Onda T, Watanabe A, Kosaki K, Nishimura K, Ohtaka M, Nakanishi M, Sakamoto T, Yamaguchi A, Sueishi K, Azuma T
    • Journal Title

      Stem Cell Res Ther

      Volume: 9 Issue: 1 Pages: 12-12

    • DOI

      10.1186/s13287-017-0754-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gorlin syndrome-derived induced pluripotent stem cells are hypersensitive to Hedgehog-mediated osteogenic induction.2017

    • Author(s)
      Hasegawa D, Shino H, Onodera S, Nakamura T, Saito A, Onda T, Watanabe K, Nishimura K, Ohtaka M, Nakanishi M, Kosaki K, Yamaguchi A, Shibahara T, Azuma T
    • Journal Title

      PLos One

      Volume: 12 Issue: 10 Pages: e0186879-e0186879

    • DOI

      10.1371/journal.pone.0186879

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of the combined use of enamel matrix derivative and atelocollagen sponge scaffold on osteoblastic differentiation of mouse induced pluripotent stem cells in vitro2017

    • Author(s)
      Hisanaga Y.、Suzuki E.、Aoki H.、Sato M.、Saito A.、Saito A.、Azuma T.
    • Journal Title

      Journal of periodontal research

      Volume: 53 Issue: 2 Pages: 240-249

    • DOI

      10.1111/jre.12511

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multi-layered mutatin in hedgehog-related genes in Gorlin syndrome may affect the phenotype.2017

    • Author(s)
      Onodera S, Saito A, Hasegawa D, Watanabe K, Morita N, Nomura T, Shibahara T, Ohba S, Yamaguchi A, Azuma T
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 9 Pages: e0184702-e0184702

    • DOI

      10.1371/journal.pone.0184702

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 鎖骨頭蓋骨異形成症由来iPS細胞を用いたRUNX2機能不全と核膜形態異常との関連2018

    • Author(s)
      齋藤暁子,大木章生,澤田隆,中村貴,小野寺晶子,長谷川大悟,小崎健次郎, 末石研二,東俊文
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 鎖骨頭蓋骨異形成症患者由来iPS細胞の解析と骨組織分化との関連の検討2017

    • Author(s)
      齋藤暁子,大木章生,中村貴,小野寺晶子,篠宏美,長谷川大悟,小崎健次郎,恩田健志,渡邊 章,柴原孝彦,末石研二,東俊文
    • Organizer
      第35回日本骨代謝学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] iPS細胞を用いた顎骨疾患病態解明へのアプローチ2017

    • Author(s)
      東俊文
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 鎖骨頭蓋異形成症iPS細胞の核形態変化と核内マトリックスタンパク質異常のゲノム編集による正常化2016

    • Author(s)
      東俊文,寺田総一郎
    • Organizer
      第48回日本臨床分子形態学会総会・学術大会
    • Place of Presentation
      熊本市
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Analyses of osteogenic differentiation in iPS cells derived from cleidocranial dysplasia patients2016

    • Author(s)
      Saito A, Oki A, Nakamura T, Onodera S, Shino H, Hasegawa D, Kosaki K, Onda T, Watanabe A, Shibahara T, Sueishi K, Azuma T
    • Organizer
      The joint annual scientific meetings of the endocrine society of Australia, the society for reproductive biology and the Australian and new Zealand bone and mineral society
    • Place of Presentation
      Gold Coast
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 鎖骨頭蓋骨異形成症患者由来iPS細胞の解析と骨組織分化との関連の検討2016

    • Author(s)
      齋藤暁子,大木章生,中村貴,小野寺晶子,篠宏美,長谷川大悟,小崎健次郎,恩田 健志,渡邊 章,柴原孝彦,末石研二,東俊文
    • Organizer
      第34回日本骨代謝学会学術集会
    • Place of Presentation
      大阪市
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] 鎖骨頭蓋骨異形成症患者由来細胞を用いた疾患特異的iPS細胞の樹立と機能解析2016

    • Author(s)
      大木章生,坂本輝雄,長谷川大悟,柴原孝彦,東俊文,末石研二
    • Organizer
      第26回日本顎変形症学会総会・学術大会
    • Place of Presentation
      東京都
    • Year and Date
      2016-06-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Runx2ホモ欠損マウス由来iPS細胞を用いた骨芽細胞分化機構におけるRunx2非依存的経路の解析2016

    • Author(s)
      青木栄人,鈴木瑛一,久永幸乃,佐藤正敬,小野寺晶子,篠宏美,齋藤暁子,齋藤淳,東俊文
    • Organizer
      第301回東京歯科大学学会・例会
    • Place of Presentation
      東京都
    • Year and Date
      2016-06-04
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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