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Developmental contribution of growth plate-derived hedgehog signal-responsive cells in bone marrow development

Research Project

Project/Area Number 18K06832
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionEhime University

Principal Investigator

Haraguchi Ryuma  愛媛大学, 医学系研究科, 准教授 (00423690)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords成長版 / 組織系譜解析 / ヘッジホッグシグナル / 造血ニッチ / 骨髄 / Hhシグナル / 成長板 / 骨髄ニッチ / 造血幹細胞 / ヘッジホッグ / 遺伝子改変マウス
Outline of Final Research Achievements

Longitudinal bone growth progresses by continuous bone replacement of epiphyseal cartilaginous tissue, known as “growth plate”, produced by columnar proliferated- and differentiated-epiphyseal chondrocytes. The endochondral ossification process at the growth plate is governed by paracrine signals secreted from terminally differentiated chondrocytes (hypertrophic chondrocytes), and hedgehog signaling is one of the best known regulatory signaling pathways in this process. To investigate the developmental relationship between longitudinal endochondral bone formation and osteogenic progenitors under the influence of hedgehog signaling at the growth plate, genetic lineage tracing was carried out with the use of Gli1CreERT2 mice line. Our results show an evidence of the developmental contribution of endochondral progenitors under the influence of epiphyseal chondrocyte-derived secretory signals in bone marrow formation.

Academic Significance and Societal Importance of the Research Achievements

骨髄は、白血病、多発性骨髄腫、再生不良性貧血などの難治性造血器疾患の罹患臓器であるが、これまで造血幹細胞を含む血液細胞を主体とした研究がなされてきた。しかし、近年の造血幹細胞を支持する非血液細胞(ニッチ)の同定により、造血器疾患における造血ニッチの関与が注目され始めている。本研究の遂行により得られた成果は、未だに未知の難治性造血器疾患の発症機序解明や造血ニッチを標的とする新しい視点からの治療法確立などに貢献する可能性があり、学術のみならず社会への波及効果も強く期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (23 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 11 results,  Open Access: 8 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] New Insights into Development of Female Reproductive Tract-Hedgehog-Signal Response in Wolffian Tissues Directly Contributes to Uterus Development2021

    • Author(s)
      Haraguchi Ryuma、Yamada Gen、Murashima Aki、Matsumaru Daisuke、Kitazawa Riko、Kitazawa Sohei
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 3 Pages: 1211-1211

    • DOI

      10.3390/ijms22031211

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Localization of DLL1- and NICD-positive osteoblasts in cortical bone during postnatal growth in rats.2020

    • Author(s)
      Kohara Y, Kitazawa S, Kitazawa R, Haraguchi R, Arai K, Amasaki H, Soeta S.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 529 Issue: 2 Pages: 186-190

    • DOI

      10.1016/j.bbrc.2020.06.039

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hedgehog inhibitors suppress osteoclastogenesis in in vitro cultures, and deletion of smo in macrophage/osteoclast lineage prevents age-related bone loss.2020

    • Author(s)
      Kohara Y, Haraguchi R, Kitazawa R, Imai Y, Kitazawa S.
    • Journal Title

      Int J Mol Sci

      Volume: 21 Issue: 8 Pages: 2745-2745

    • DOI

      10.3390/ijms21082745

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] New insights into the pathogenesis of diabetic nephropathy: proximal renal tubules are primary target of oxidative stress in diabetic kidney2020

    • Author(s)
      Haraguchi Ryuma、Kohara Yukihiro、Matsubayashi Kanako、Kitazawa Riko、Kitazawa Sohei
    • Journal Title

      Acta histochemica et cytochemica

      Volume: in press

    • NAID

      130007836959

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Knockdown of Lrp1 in RAW264?cells inhibits osteoclast differentiation and osteoclast-osteoblast interactions in?vitro2020

    • Author(s)
      Kohara Yukihiro、Haraguchi Ryuma、Kitazawa Riko、Kitazawa Sohei
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 523 Issue: 4 Pages: 961-965

    • DOI

      10.1016/j.bbrc.2020.01.065

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modulation of α<sub>v</sub>β<sub>3</sub> Integrin via Transactivation of β<sub>3</sub> Integrin Gene on Murine Bone Marrow Macrophages by 1,25(OH)<sub>2</sub>D<sub>3</sub>, Retinoic Acid and Interleukin-42019

    • Author(s)
      Kitazawa Sohei、Haraguchi Ryuma、Kohara Yukihiro、Kitazawa Riko
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 52 Issue: 4 Pages: 77-83

    • DOI

      10.1267/ahc.19015

    • NAID

      130007696918

    • ISSN
      0044-5991, 1347-5800
    • Year and Date
      2019-08-30
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hedgehog Signaling for Urogenital Organogenesis and Prostate Cancer: An Implication for the Epithelial?Mesenchyme Interaction (EMI)2019

    • Author(s)
      Hyuga Taiju、Alcantara Mellissa、Kajioka Daiki、Haraguchi Ryuma、Suzuki Kentaro、Miyagawa Shinichi、Kojima Yoshiyuki、Hayashi Yutaro、Yamada Gen
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 1 Pages: 58-58

    • DOI

      10.3390/ijms21010058

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recent Insights into Long Bone Development: Central Role of Hedgehog Signaling Pathway in Regulating Growth Plate2019

    • Author(s)
      Haraguchi、Kitazawa、Kohara、Ikedo、Imai、Kitazawa
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 23 Pages: 5840-5840

    • DOI

      10.3390/ijms20235840

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Activation of protein kinase C accelerates murine osteoclastogenesis partly via transactivation of RANK gene through functional AP-1 responsive element in RANK gene promoter2019

    • Author(s)
      Kitazawa Riko、Kinto-Shibahara Satomi、Haraguchi Ryuma、Kohara Yukihiro、Kitazawa Sohei
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 515 Issue: 2 Pages: 268-274

    • DOI

      10.1016/j.bbrc.2019.05.144

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 骨巨細胞腫の病態と治療修飾2019

    • Author(s)
      北澤荘平、木谷彰岐、原口竜摩、北澤理子.
    • Journal Title

      愛媛医学

      Volume: 38 Pages: 1-6

    • Related Report
      2018 Research-status Report
  • [Journal Article] Morphology-oriented epigenetic research.2018

    • Author(s)
      Kitazawa S, Haraguchi R, Kitazawa R.
    • Journal Title

      Histochem Cell Biol.

      Volume: 150(1) Issue: 1 Pages: 3-12

    • DOI

      10.1007/s00418-018-1675-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Regulation of masculinization: androgen signalling for external genitalia development2018

    • Author(s)
      Matsushita Shoko、Suzuki Kentaro、Murashima Aki、Kajioka Daiki、Acebedo Alvin Resultay、Miyagawa Shinichi、Haraguchi Ryuma、Ogino Yukiko、Yamada Gen
    • Journal Title

      Nature Reviews Urology

      Volume: 印刷中 Issue: 6 Pages: 358-368

    • DOI

      10.1038/s41585-018-0008-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] ヘッジホッグシグナル調節因子Hhipの骨形成過程における役割2020

    • Author(s)
      原口竜摩、小原幸弘、北澤理子、北澤荘平
    • Organizer
      第109回 日本病理学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 成長板を発生起点とする骨髄微小環境形成メカニズムの解析2020

    • Author(s)
      原口竜摩
    • Organizer
      第38回 日本骨代謝学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ヘッジホッグシグナル調節因子Hhipの骨形成過程における役割2020

    • Author(s)
      原口竜摩、小原幸弘、北澤理子、北澤荘平
    • Organizer
      第61回 日本組織細胞化学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Specific role of Hh signaling pathway in bone resorption2020

    • Author(s)
      Ryuma Haraguchi, Yukihiro Kohara, Riko Kitazawa, Yuuki Imai, Sohei Kitazawa
    • Organizer
      ASBMR 2020 Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 近位尿細管に注目したストレプトゾトシン誘導性糖尿病腎の病態組織学的考察2019

    • Author(s)
      原口竜摩、松林加那子、北澤理子、北澤荘平
    • Organizer
      第108回 日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヘッジホッグシグナル調節因子Hhipの骨形成過程における役割2019

    • Author(s)
      原口竜摩、小原幸弘、今井祐記、北澤理子、北澤荘平
    • Organizer
      第37回 日本骨代謝学会
    • Related Report
      2019 Research-status Report
  • [Presentation] ストレプトゾトシン誘導性糖尿病腎における腎尿細管に注目した病理組織学的考察2019

    • Author(s)
      原口竜摩、小原幸弘、松林加那子、北澤理子、北澤荘平
    • Organizer
      第60回 日本組織細胞化学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Developmental contribution of growth plate-derived hedgehog signal-responsive cells in growing bone2018

    • Author(s)
      Ryuma Haraguchi, Riko Kitazawa, Yuuki Imai, Sohei Kitazawa
    • Organizer
      ASBMR 2018 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 成長板に由来するヘッジホッグシグナル受容細胞の骨格発生における役割2018

    • Author(s)
      原口竜摩、北澤理子、北澤荘平
    • Organizer
      第107回 日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 成長板を発生起点とするヘッジホッグシグナル受容細胞の骨格形成への関与2018

    • Author(s)
      原口竜摩、北澤理子、今井祐記、北澤荘平
    • Organizer
      第36回 日本骨代謝学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヘッジホッグシグナルを介する成長板を発生起点とした骨格形成の理解2018

    • Author(s)
      原口竜摩、北澤理子、北澤荘平
    • Organizer
      第59回 日本組織細胞化学会
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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