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Differentiation Mechanism of Osteoclast revealed by single cell and 3D structure analysis

Research Project

Project/Area Number 20K22973
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0906:Surgery related to the biological and sensory functions and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Okada Hiroyuki  東京大学, 大学院医学系研究科(医学部), 助教 (10883481)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords破骨細胞 / 1細胞解析 / シングルセル / 多核巨細胞 / シングルセル解析 / 転写制御
Outline of Research at the Start

骨粗鬆症治療薬にはアンメットニーズが素材する。骨を壊す破骨細胞について、いまだに残された分化の謎を解き明かす。
最新のシングルセル解析および転写因子立体構造解析を行い、多核の巨細胞がどのように遺伝子の発現、転写を制御しているのか、メカニズムを解明する。新たな骨粗鬆症治療薬創出のターゲットを探索する。

Outline of Final Research Achievements

With traditional method of gene expression, we can only obtain the average value of gene expression. Single cell analysis reveals the diversity of gene expression cell by cell. We adapt single cell technology to researches of osteoclast. With commercially available method, we cannot capture giant mature osteoclast. We fortunately got support from advanced genome platform in Japan, we have developed the platform to catch and detect mature osteoclast.
In addition, we built mouse bone atlas with public dataset of single cell analysis on bone and bone marrow.
Taken together, we got key factors involving bone remodeling process. These findings will clarify the novel target of osteoporosis and skeletal diseases.

Academic Significance and Societal Importance of the Research Achievements

高齢社会日本において、骨粗しょう症に起因する脆弱性骨折患者の生命および機能予後改善は、医療・介護の重要課題である。現存する骨粗鬆症治療薬では、全ての高齢者を安全に治療できないため、「速やかに」かつ「安全に」骨密度を改善する新規薬剤の開発が求められている。
本研究の研究成果は、新たな骨粗しょう症創薬ターゲット探索に寄与するものである。スタートアップ支援で得た知見をもとに、臨床応用を見据え研究を加速させる所存である。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (16 results)

All 2022 2021 2020

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results)

  • [Journal Article] Plasmalemmal interface for calcium signaling in osteoclast differentiation2022

    • Author(s)
      Okada Hiroyuki、Tanaka Sakae
    • Journal Title

      Current Opinion in Cell Biology

      Volume: 74 Pages: 55-61

    • DOI

      10.1016/j.ceb.2022.01.001

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcription Factor Hematopoietically Expressed Homeobox Protein (Hhex) Negatively Regulates Osteoclast Differentiation by Controlling Cyclin‐Dependent Kinase Inhibitors2022

    • Author(s)
      Watanabe Hisato、Okada Hiroyuki、Hirose Jun、Omata Yasunori、Matsumoto Takumi、Matsumoto Morio、Nakamura Masaya、Saito Taku、Miyamoto Takeshi、Tanaka Sakae
    • Journal Title

      JBMR Plus

      Volume: 6 Issue: 4

    • DOI

      10.1002/jbm4.10608

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesenchymal stromal cells in the bone marrow niche consist of multi-populations with distinct transcriptional and epigenetic properties2021

    • Author(s)
      Kanazawa Sanshiro、Okada Hiroyuki、Hojo Hironori、Ohba Shinsuke、Iwata Junichi、Komura Makoto、Hikita Atsuhiko、Hoshi Kazuto
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 15811-15811

    • DOI

      10.1038/s41598-021-94186-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Progress of Stem Cell Technology for Skeletal Regeneration2021

    • Author(s)
      Tani Shoichiro、Okada Hiroyuki、Chung Ung-il、Ohba Shinsuke、Hojo Hironori
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 3 Pages: 1404-1404

    • DOI

      10.3390/ijms22031404

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Finely-Tuned Calcium Oscillations in Osteoclast Differentiation and Bone Resorption2020

    • Author(s)
      Okada Hiroyuki、Okabe Koji、Tanaka Sakae
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 1 Pages: 180-180

    • DOI

      10.3390/ijms22010180

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] single cell Bone Milieu Atlas作成とその利活用2022

    • Author(s)
      岡田寛之、谷彰一郎、小俣康徳、寺島明日香、矢野文子*3、斎藤琢*2、田中栄*2、鄭雄一*1、北條宏徳*1
    • Organizer
      第6回日本骨免疫学会ウィンタースクール
    • Related Report
      2021 Annual Research Report
  • [Presentation] 1細胞レベルで理解する骨の生理・病理2021

    • Author(s)
      岡田寛之, 鍛治屋浩、小俣康徳、北條宏徳、鄭雄一、岡部幸司、宮本健史、田中栄
    • Organizer
      福岡歯科大学口腔医学研究センターシンポジウム「口腔医学研究のRising Sunに出会う」
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 数理モデルが解き明かす破骨細胞分化に必須な共刺激2021

    • Author(s)
      岡田寛之、鍛治屋浩、小俣康徳、北條宏徳、鄭雄一、岡部幸司、宮本健史、田中栄
    • Organizer
      第36回日本整形外科学会基礎学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 数理モデルが解き明かす破骨細胞分化における細胞内カルシウム動態 - CTLA4-Igの骨破壊抑制機序を含めて2021

    • Author(s)
      岡田寛之、鍛治屋浩、小俣康徳、北條宏徳、鄭雄一、岡部幸司、宮本健史、田中栄
    • Organizer
      第39回日本骨代謝学会 日本リウマチ学会合同シンポジウム「関節リウマチにおける関節破壊機序」
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] RANKLとITAMが生み出す破骨細胞のカルシウムハーモニー2021

    • Author(s)
      岡田寛之、鍛治屋浩、小俣康徳、北條宏徳、鄭雄一、岡部幸司、宮本健史、田中栄
    • Organizer
      第6回日本骨免疫学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Frequency and amplitude analyses of calcium oscillations reveals the harmony regulated by ITAM receptors during RANKL-induced osteoclastogenesis2021

    • Author(s)
      Hiroyuki Okada, Hiroshi Kajiya, Yasunori Omata, Hironori Hojo, Ung-il Chung, Koji Okabe, Takeshi Miyamoto, Sakae Tanaka
    • Organizer
      ECTS (european calcified tissue society) 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 破骨細胞分化におけるカルシウム振動制御の妙2021

    • Author(s)
      岡田寛之、鍛治屋浩、小俣康徳、北條宏徳、鄭雄一、岡部幸司、宮本健史、田中栄
    • Organizer
      第18回 Osteoimmunology Forum
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Atlas of murine bone milieu provides insights into cell-cell interaction between osteoclast, osteoblast, and osteocyte in bone remodeling2021

    • Author(s)
      Hiroyuki Okada, Shoichiro Tani, Mika Nakayama, Dahlia Eldeeb, Yasunori Omata, Fumiko Yano, Taku Saito, Sakae Tanaka, Shinsuke Ohba, Ung-il Chung, Hironori Hojo
    • Organizer
      ASBMR (American Society for Bone and Mineral Research) 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dectin-2, a Fc receptor gamma-harboring receptor, regulates foreign body reaction by interfering with intracellular calcium oscillation.2020

    • Author(s)
      Hiroyuki Okada, Hiroshi Kajiya, Yasunori Omata, Koji Okabe, Takeshi Miyamoto, Sakae Tanaka
    • Organizer
      ASBMR 2020 Annual Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 破骨細胞分化初期の共刺激-カルシウムオシレーション-NFATc1 軸 ~特に共刺激周囲の補因子について2020

    • Author(s)
      岡田寛之、鍛治屋浩、小俣康徳、岡部幸司、宮本健史、田中栄
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Dectin-2はFcRγと会合し、カルシウム振動に干渉し異物反応を制御する2020

    • Author(s)
      岡田寛之、鍛治屋浩、小俣康徳、岡部幸司、宮本健史、田中栄
    • Organizer
      第38回日本骨代謝学会
    • Related Report
      2020 Research-status Report

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Published: 2020-09-29   Modified: 2023-01-30  

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