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Understanding of Runx2-mediated hierarichical gene regulatory network in bone formation and application of the network for bone regeneration

Research Project

Project/Area Number 17H05106
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Surgical dentistry
Research InstitutionThe University of Tokyo

Principal Investigator

Hojo Hironori  東京大学, 大学院医学系研究科(医学部), 准教授 (80788422)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2017: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Keywords転写制御 / 骨発生 / Runx2 / エピゲノム / 転写因子 / 発生・分化 / 発現制御 / バイオインフォマティクス / 骨形成
Outline of Final Research Achievements

Runx2 is an essential transcription factor for both osteoblast specification and chondrocyte hypertrophy. In this study, we performed integrative analysis of Runx2-DNA binding profile and cell-type distinct epigenetic landscape profile in mouse neonatal osteoblasts and chondrocytes. We identified cell-type specific putative enhancers targeted by Runx2 in osteoblasts and chondrocytes, and confirmed a biological function of these. Through this study, we identified a Runx2-mediated gene regulatory program in skeletal development.

Academic Significance and Societal Importance of the Research Achievements

転写因子Runx2は骨を形成する骨芽細胞の分化決定・成熟化を促進する作用と、軟骨組織に存在する軟骨細胞の分化・肥大化を進める作用を有しており、これらのメカニズム解明は、骨格組織の再生医療法の確立や疾患の分子病態の理解に必須である。本研究では、Runx2の骨芽細胞と軟骨細胞に対する作用メカニズムの一端を、ゲノムワイドな転写制御機構の観点から明らかにし、骨格再生に向けた基礎的知見を取得した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (17 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (9 results) (of which Int'l Joint Research: 8 results)

  • [Int'l Joint Research] 南カリフォルニア大学/マサチューセッツ総合病院/アメリカ国立衛生研究所(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Stepwise strategy for generating osteoblasts from human pluripotent stem cells under fully defined xeno-free conditions with small-molecule inducers2020

    • Author(s)
      Zujur Denise、Kanke Kosuke、Onodera Shoko、Tani Shoichiro、Lai Jenny、Azuma Toshifumi、Xin Xiaonan、Lichtler Alexander C.、Rowe David W.、Saito Taku、Tanaka Sakae、Masaki Hideki、Nakauchi Hiromitsu、Chung Ung-il、Hojo Hironori、Ohba Shinsuke
    • Journal Title

      Regenerative Therapy

      Volume: 14 Pages: 19-31

    • DOI

      10.1016/j.reth.2019.12.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Insights into Gene Regulatory Networks in Chondrocytes2019

    • Author(s)
      Hojo Hironori、Ohba Shinsuke
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 24 Pages: 6324-6324

    • DOI

      10.3390/ijms20246324

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Wnt/β-catenin signaling contributes to articular cartilage homeostasis through lubricin induction in the superficial zone2019

    • Author(s)
      Xuan Fengjun、Yano Fumiko、Mori Daisuke、Chijimatsu Ryota、Maenohara Yuji、Nakamoto Hideki、Mori Yoshifumi、Makii Yuma、Oichi Takeshi、Taketo Makoto Mark、Hojo Hironori、Ohba Shinsuke、Chung Ung-il、Tanaka Sakae、Saito Taku
    • Journal Title

      Arthritis Research & Therapy

      Volume: 21 Issue: 1 Pages: 247-247

    • DOI

      10.1186/s13075-019-2041-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Simple and Robust Differentiation of Human Pluripotent Stem Cells toward Chondrocytes by Two Small-Molecule Compounds2019

    • Author(s)
      Kawata Manabu、Mori Daisuke、Kanke Kosuke、Hojo Hironori、Ohba Shinsuke、Chung Ung-il、Yano Fumiko、Masaki Hideki、Otsu Makoto、Nakauchi Hiromitsu、Tanaka Sakae、Saito Taku
    • Journal Title

      Stem Cell Reports

      Volume: 13 Issue: 3 Pages: 530-544

    • DOI

      10.1016/j.stemcr.2019.07.012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of orthotopically functional salivary gland from embryonic stem cells2018

    • Author(s)
      Tanaka Junichi、Ogawa Miho、Hojo Hironori、Kawashima Yusuke、Mabuchi Yo、Hata Kenji、Nakamura Shiro、Yasuhara Rika、Takamatsu Koki、Irie Tarou、Fukada Toshiyuki、Sakai Takayoshi、Inoue Tomio、Nishimura Riko、Ohara Osamu、Saito Ichiro、Ohba Shinsuke、Tsuji Takashi、Mishima Kenji
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 4216-4216

    • DOI

      10.1038/s41467-018-06469-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of the gene-regulatory landscape in skeletal development and potential links to skeletal regeneration.2017

    • Author(s)
      Hojo H, Chung UI, Ohba S
    • Journal Title

      Regenerative Therapy

      Volume: 6 Pages: 100-107

    • DOI

      10.1016/j.reth.2017.04.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Three-dimensional system enabling the maintenance and directed differentiation of pluripotent stem cells under defined conditions2017

    • Author(s)
      Zujur D, Kanke K, Lichtler AC, Hojo H, Chung UI, Ohba S
    • Journal Title

      Science Advanvces

      Volume: 3 Issue: 5

    • DOI

      10.1126/sciadv.1602875

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Cell-type-distinct regulatory action of Runx2 on the genome underlies its distinct roles in osteoblasts and chondrocytes.2019

    • Author(s)
      Hojo H, Ohba S, Yamakawa A, Guo Q, He X, Saito T, Onodera S, Azuma T, Chung UI, McMahon AP.
    • Organizer
      2019 Annual Meeting of the American Society for Bone and Mineral Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] De novo missense mutation in SP7 in a patient with cranial hyperostosis, long bone fragility, and increased osteoblast number.2019

    • Author(s)
      Lui J, Raimann A, Dong L, Hojo H, Roschger P, Fratzl-Zelman N, Jee YH, Haeusler G, Baron J
    • Organizer
      2019 Annual Meeting of the American Society for Bone and Mineral Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A Novel SP7/OSTN Axis Controls Osteocyte Morphology and Function2019

    • Author(s)
      Wang JS, Mirzamohammadi F, Hojo H, Rotter D, Castro Andrade CD, Fiscaletti M, Kronenberg HM, Wein MN
    • Organizer
      2019 Annual Meeting of the American Society for Bone and Mineral Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Runx2は骨格発生において細胞種特異的な転写制御領域に作用する2019

    • Author(s)
      1.北條宏徳、山川晃、齋藤琢、小野寺晶子、東俊文、鄭雄一、大庭伸介
    • Organizer
      第37回日本骨代謝学会学術集会,
    • Related Report
      2019 Annual Research Report
  • [Presentation] Identification of a chondrocyte-specific Indian hedgehog enhancer and Sox9-mediated mechanisms of the enhancer activation2018

    • Author(s)
      Yamakawa A, Hojo H, Chung UI, Ohba S
    • Organizer
      OARSI World Congress on Osteoarthritis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of Osterix (SP7) in Regulating Osteocyte Biology and Dendrite Formation2018

    • Author(s)
      Mirzamohammadi F, Hojo H, Enishi T, Govea N, Kronenberg HM, Wein MN
    • Organizer
      2018 Annual Meeting of the American Society for Bone and Mineral Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Modeling of bone remodeling by three-dimensional co-culture of mouse embryonic stem cell-derived osteoblasts and osteoclast precursors2017

    • Author(s)
      Zujur DC, Hikita A, Kanke K, Hojo H, Chung UI, Ohba S
    • Organizer
      International Society for Stem Cell Research 15th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vivo bone formation by osteoblasts generated from human induced pluripotent stem cells under fully defined xeno-free conditions2017

    • Author(s)
      Zujur DC, Kanke K, Hojo H, Onodera S, Azuma T, Chung UI, Ohba S
    • Organizer
      39th Annual Meeting of the American Society for Bone and Mineral Research
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A system level investigation to unravel mechanisms and potential direct targets of the osteogenic small molecule TH2017

    • Author(s)
      Ichsan M, Kanke K, Hojo H, Chung UI, Ohba S
    • Organizer
      EMBL Conference: Mammalian Genetics and Genomics
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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