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Elucidation of mechanical stress response mechanism using imaging analysis of genetically modified zebrafish

Research Project

Project/Area Number 19KK0233
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 57:Oral science and related fields
Research InstitutionShowa University

Principal Investigator

Chatani Masahiro  昭和大学, 歯学部, 准教授 (80628628)

Project Period (FY) 2019-10-07 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2021: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2020: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsゼブラフィッシュ / メダカ / 骨 / 血管 / 血球細胞 / 血球 / 心臓 / メカニカルストレス / 器官形成
Outline of Research at the Start

人が宇宙に行くと骨量減少、筋量減少、心機能低下など様々な障害が発生する。これは重力が無くなることで体内の器官に働いていたメカニカルストレスに変化が生じ、器官の恒常性維持機構が破綻したためと考えられるが、詳細なメカニズムはまだわかっていない。申請者らはメダカの骨研究モデルを用いた国際宇宙ステーション飼育研究の経験を活かし、小型魚類におけるメカニカルストレス応答能を有する器官形成機構の一端を解明する。そのため申請者はマックス・プランク心臓肺研究所所長のDr. Stainierと共同研究を行い、ゼブラフィッシュまたはメダカの遺伝子改変体を駆使したメカニカルストレス応答器官の研究を遂行する。

Outline of Final Research Achievements

We focused on the cloche zebrafish mutant. We generated npas4l gene-deficient medaka to elucidate the mechanism conserved across species. The npas4l-deficient medaka exhibited a marked decrease in hematopoietic and vascular endothelial cells. Single-cell RNA-seq analysis identified a cell population expressing both hematopoietic and vascular endothelial cell markers, and gene expression analysis suggested that hemangioblasts were localized around the early embryo. In addition, dysplasia of some bones was observed, suggesting the involvement of blood vessels in hard tissue formation. The enhancers that function during fin regeneration in zebrafish were analyzed in medaka, and an enhancer that is strongly expressed during fin regeneration in medaka was identified. It is expected to elucidate the mechanism of hard tissue regeneration that is conserved across species.

Academic Significance and Societal Importance of the Research Achievements

本研究で小型魚類を用いることで血球と血管の両者に共通な前駆細胞である血球血管芽細胞の存在を示唆し、それに関する遺伝子発現のデータベースを構築できた点で学術的意義がある。また血管、血球、一部の骨を欠失した変異体を作出しており、その解析から生体内メカニカルストレスの受容メカニズム解明が期待される。血球血管芽細胞はヒトにも存在する幹細胞と考えられており、その分化メカニズム解明により関連疾患の解決が期待されるという点で社会的意義がある。種を超えて保存されている、組織の再生に重要なエンハンサー領域を明らかにすることは、再生医学においても重要な課題であり、将来的に再生医療への貢献が期待される。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (17 results)

All 2024 2023 2020 Other

All Int'l Joint Research (2 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] Max Planck institute(ドイツ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] MPI for Heart and Lung Research(ドイツ)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Abnormal bone regeneration induced by FK506 in medaka fin revealed by in vivo imaging2024

    • Author(s)
      Kai Otake, Yuki Azetsu, Masahiro Chatani, Akiko Karakawa, Satoko Nishida, Aiko Hirayama, Rina Kobayashi, Nobuhiro Sakai, Noriyuki Suzuki, Masamichi Takami
    • Journal Title

      J Oral Biosci.

      Volume: - Issue: 2 Pages: 381-390

    • DOI

      10.1016/j.job.2024.02.007

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tacrolimus, FK506, promotes bone formation in bone defect mouse model2024

    • Author(s)
      Satoko Nishida, Yuki Azetsu, Masahiro Chatani, Akiko Karakawa, Kai Otake, Hidemitsu Sugiki, Nobuhiro Sakai, Yasubumi Maruoka, Mie Myers, Masamichi Takami
    • Journal Title

      J Oral Biosci.

      Volume: - Issue: 2 Pages: 391-402

    • DOI

      10.1016/j.job.2024.02.003

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Behavior of intracellular lipid droplets during cell division in HuH7 hepatoma cells2023

    • Author(s)
      Tomohiko Makiyama, Takashi Obama, Yuichi Watanabe, Masahiro Chatani, Yuki Azetsu, Kosuke Kawaguchi, Tsuneo Imanaka, Hiroyuki Itabe
    • Journal Title

      Exp Cell Res.

      Volume: 433 Issue: 2 Pages: 113855-113855

    • DOI

      10.1016/j.yexcr.2023.113855

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Myelination during fracture healing in vivo in myelin protein zero (p0) transgenic medaka line2020

    • Author(s)
      Dodo Y, Chatani M, Azetsu Y, Hosonuma M, Karakawa A, Sakai N, Negishi-Koga T, Tsuji M, Inagaki K, Kiuchi Y, Takami M
    • Journal Title

      Bone

      Volume: 133 Pages: 115225-115225

    • DOI

      10.1016/j.bone.2020.115225

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] メダカからひも解く骨の科学2020

    • Author(s)
      畔津佑季、百々悠介、髙見正道、茶谷昌宏
    • Journal Title

      整形・災害外科

      Volume: 63, 10 Pages: 1417-1422

    • Related Report
      2020 Research-status Report
  • [Presentation] メダカを用いた宇宙と地上の骨生物学研究2023

    • Author(s)
      茶谷昌宏
    • Organizer
      第70回日本実験動物学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Investigating Npas4l/Cloche in Medaka (Oryzias latipes) for Understanding the Developmental Mechanisms of Blood and Blood Vessel Formation.2023

    • Author(s)
      Masahiro Chatani
    • Organizer
      Institutional Seminar Series
    • Related Report
      2023 Annual Research Report
  • [Presentation] Cloche/Npas4l is Essential for Hematopoiesis and Vasculogenesis in Medaka2023

    • Author(s)
      M Chatani, J Martinez, D Stainier.
    • Organizer
      International Institute Evaluation by the Scientific Advisory Board
    • Related Report
      2023 Annual Research Report
  • [Presentation] New type of TRAP-positive cell contributes to actinotrichia degradation during fin fold formation2020

    • Author(s)
      Masahiro Chatani, Shunsuke Kobayashi, Takashi Takaki, Masamichi Takami
    • Organizer
      11th EUROPEAN ZEBRAFISH 2020 VIRTUAL MEETING
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 遺伝子改変メダカを用いた鰭の原繊維を壊す細胞の探索2020

    • Author(s)
      茶谷昌宏、小林俊介、高木孝士、高見正道
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 高コレステロール食によって誘発されるマウス骨量低下の解析2020

    • Author(s)
      佐藤ゆり絵,坂井信裕,黒滝優太朗,細沼雅弘,唐川亜希子,畔津佑季,茶谷昌宏,髙見正道
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 遺伝子改変メダカを用いた骨折治癒過程における髄鞘と骨芽細胞の機能解明2020

    • Author(s)
      百々 悠介、茶谷 昌宏、石川 紘司、畔津 佑季、永井 隆士、木内 祐二、高見 正道、稲垣 克記
    • Organizer
      第40回日本骨形態計測学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 骨および歯の恒常性維持におけるグルココルチコイド受容体の機能-遺伝子改変メダカを用いた解析-2020

    • Author(s)
      畔津 佑季、茶谷 昌宏、唐川 亜希子、坂井 信裕、髙見 正道
    • Organizer
      第142回 日本薬理学会関東部会
    • Related Report
      2020 Research-status Report
  • [Presentation] 抗RANKL抗体とゾレドロネートがマウスの歯の恒常性に及ぼす薬理作用の比較2020

    • Author(s)
      唐川 亜希子、坂井 信裕、茶谷 昌宏、髙見 正道
    • Organizer
      第142回 日本薬理学会関東部会
    • Related Report
      2020 Research-status Report
  • [Presentation] 脂質の過量摂取が歯の恒常性維持機構に及ぼす影響2020

    • Author(s)
      坂井 信裕、黒滝 優太朗、佐藤 ゆり絵、畔津 佑季、唐川 亜希子、茶谷 昌宏、髙見 正道
    • Organizer
      第142回 日本薬理学会関東部会
    • Related Report
      2020 Research-status Report

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Published: 2019-10-10   Modified: 2025-01-30  

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