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Development of innovative medical technology based on integrated understanding of both protection and destruction of articular cartilage homeostasis.

Research Project

Project/Area Number 16H06393
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionOsaka University

Principal Investigator

Nishimura Riko  大阪大学, 歯学研究科, 教授 (60294112)

Co-Investigator(Kenkyū-buntansha) 村上 智彦  大阪大学, 歯学研究科, 講師 (50510723)
高畑 佳史  大阪大学, 歯学研究科, 助教 (60635845)
波多 賢二  大阪大学, 歯学研究科, 准教授 (80444496)
Project Period (FY) 2016-05-31 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥181,870,000 (Direct Cost: ¥139,900,000、Indirect Cost: ¥41,970,000)
Fiscal Year 2020: ¥37,440,000 (Direct Cost: ¥28,800,000、Indirect Cost: ¥8,640,000)
Fiscal Year 2019: ¥39,650,000 (Direct Cost: ¥30,500,000、Indirect Cost: ¥9,150,000)
Fiscal Year 2018: ¥34,840,000 (Direct Cost: ¥26,800,000、Indirect Cost: ¥8,040,000)
Fiscal Year 2017: ¥31,720,000 (Direct Cost: ¥24,400,000、Indirect Cost: ¥7,320,000)
Fiscal Year 2016: ¥38,220,000 (Direct Cost: ¥29,400,000、Indirect Cost: ¥8,820,000)
Keywords変形性関節症 / 軟骨 / 転写因子 / 細胞内シグナル / 関節軟骨細胞 / ゲノム編集 / 創薬 / 関節軟骨 / Gdf5 / Prg4 / サイトカイン / 関節軟骨生物学 / ダイレクトリプログラミング / 再生
Outline of Final Research Achievements

In this research project, to elucidate the molecular mechanism of articular cartilage homeostasis, we focused on the roles of the regulatory mechanism of gene expression and its intracellular signaling, and identified transcription factors and intracellular signaling pathways required for the formation of articular cartilage chondrocytes. We also found the mechanisms involved in the destruction of articular cartilage, which is observed in osteoarthritis and other joint diseases. Based on these findings, they succeeded in identifying target molecules and developing a screening system for drug discovery against osteoarthritis, contributing to the establishment of a foundation for therapeutic strategies for osteoarthritis.

Academic Significance and Societal Importance of the Research Achievements

これまで不明であった関節軟骨細胞の細胞生物学的および分子生物学的特性に対する理解が進展した。特に、成長軟骨細胞ではほとんど発現が観られない、関節軟骨表層細胞に特異的かつその機能に重要であるPrg4およびGdf5の発現機構を、分子、細胞、および個体レベルで解明することができた。また、Prg4遺伝子およびGdf5遺伝子を制御する転写因子ならびに細胞内シグナルを同定した。これらの研究成果は、新規性および独創性に富み高い学術的意義を有する。
また本研究により、関節軟骨細胞の再生や変形性関節症の創薬スクリーニングシステムの開発基盤を構築することができ、社会的にも重要な役割を果たすと期待される。

Assessment Rating
Verification Result (Rating)

A

Assessment Rating
Result (Rating)

A: Progress in the research is steadily towards the initial goal. Expected research results are expected.

Report

(11 results)
  • 2022 Research Progress Assessment (Verification Result) ( PDF )
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report   Abstract(Research Progress Assessment) ( PDF )   Research Progress Assessment (Result) ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Abstract ( PDF )   Comments on the Screening Results ( PDF )   Annual Research Report
  • Research Products

    (26 results)

All 2022 2021 2020 2019 2018 2017

All Journal Article (15 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (10 results) (of which Int'l Joint Research: 6 results,  Invited: 6 results) Book (1 results)

  • [Journal Article] Induction of salivary gland-like cells from epithelial tissues transdifferentiated from mouse embryonic fibroblasts2022

    • Author(s)
      Katada Ryogo、Tanaka Junichi、Takamatsu Koki、Hata Kenji、Yasuhara Rika、Ohnuma Shintaro、Takakura Ikuko、Nishimura Riko、Shirota Tatsuo、Mishima Kenji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 586 Pages: 55-62

    • DOI

      10.1016/j.bbrc.2021.11.064

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Smoc1 and Smoc2 regulate bone formation as downstream molecules of Runx22021

    • Author(s)
      Takahata Yoshifumi、Hagino Hiromasa、Kimura Ayaka、Urushizaki Mitsuki、Kobayashi Sachi、Wakamori Kanta、Fujiwara Chika、Nakamura Eriko、Yu Kayon、Kiyonari Hiroshi、Bando Kana、Murakami Tomohiko、Komori Toshihisa、Hata Kenji、Nishimura Riko
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 1199-1199

    • DOI

      10.1038/s42003-021-02717-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice2021

    • Author(s)
      Nakamura Eriko、Hata Kenji、Takahata Yoshifumi、Kurosaka Hiroshi、Abe Makoto、Abe Takaya、Kihara Miho、Komori Toshihisa、Kobayashi Sachi、Murakami Tomohiko、Inubushi Toshihiro、Yamashiro Takashi、Yamamoto Shiori、Akiyama Haruhiko、Kawaguchi Makoto、Sakata Nobuo、Nishimura Riko
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 1258-1258

    • DOI

      10.1038/s42003-021-02793-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases2020

    • Author(s)
      Nishimura Riko、Hata Kenji、Takahata Yoshifumi、Murakami Tomohiko、Nakamura Eriko、Ohkawa Maki、Ruengsinpinya Lerdluck
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 4 Pages: 1340-1340

    • DOI

      10.3390/ijms21041340

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular Mechanisms Involved in the Progression and Protection of Osteoarthritis.2020

    • Author(s)
      Takahata Y, Murakami T, Hata K, Nishimura R.
    • Journal Title

      Curr Mol Pharmacol

      Volume: 13 Issue: 2 Pages: 1-6

    • DOI

      10.2174/1874467213666200417122933

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cutting Edge: G Protein Subunit b 1 Negatively Regulates NLRP3 Inflammasome Activation2019

    • Author(s)
      Tomohiko Murakami, Lerdluck Ruengsinpinya, Eriko Nakamura,Yoshifumi Takahata, Kenji Hata, Hiroaki Okae,Shun’ichiro Taniguchi, Masafumi Takahashi and Riko Nishimura
    • Journal Title

      The Journal of Immunology

      Volume: 202 Issue: 7 Pages: 1942-1947

    • DOI

      10.4049/jimmunol.1801388

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sox4 is involved in osteoarthritic cartilage deterioration through induction of ADAMTS4 and ADAMTS52019

    • Author(s)
      Takahata Yoshifumi、Nakamura Eriko、Hata Kenji、Wakabayashi Makoto、Murakami Tomohiko、Wakamori Kanta、Yoshikawa Hiroshi、Matsuda Akio、Fukui Naoshi、Nishimura Riko
    • Journal Title

      The FASEB Journal

      Volume: 33 Issue: 1 Pages: 619-630

    • DOI

      10.1096/fj.201800259r

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [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] Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr32018

    • Author(s)
      Kawane Tetsuya、Qin Xin、Jiang Qing、Miyazaki Toshihiro、Komori Hisato、Yoshida Carolina Andrea、Matsuura-Kawata Viviane Keiko dos Santos、Sakane Chiharu、Matsuo Yuki、Nagai Kazuhiro、Maeno Takafumi、Date Yuki、Nishimura Riko、Komori Toshihisa
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 13551-13551

    • DOI

      10.1038/s41598-018-31853-0

    • NAID

      120006987946

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Interaction of LEF1 with TAZ is necessary for the osteoblastogenic activity of Wnt3a2018

    • Author(s)
      Kida Jumpei、Hata Kenji、Nakamura Eriko、Yagi Hiroko、Takahata Yoshifumi、Murakami Tomohiko、Maeda Yoshinobu、Nishimura Riko
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 10375-10375

    • DOI

      10.1038/s41598-018-28711-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptional network systems in cartilage development and disease2018

    • Author(s)
      Nishimura Riko、Hata Kenji、Nakamura Eriko、Murakami Tomohiko、Takahata Yoshifumi
    • Journal Title

      Histochem Cell Biol

      Volume: 149 Issue: 4 Pages: 353-363

    • DOI

      10.1007/s00418-017-1628-7

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung cancer in TRPV1-deficient mice.2018

    • Author(s)
      Wakabayashi H, Wakisaka S, Hiraga T, Hata K, Nishimura R, Tominaga M, Yoneda T.
    • Journal Title

      J Bone Miner Metab

      Volume: 36(3) Issue: 3 Pages: 274-285

    • DOI

      10.1007/s00774-017-0842-7

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 軟骨の発生と恒常性維持機構のメカニズム2018

    • Author(s)
      西村 理行、波多 賢二、中村 恵理子
    • Journal Title

      Clinical Calcium

      Volume: 28 Pages: 353-359

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Regulation of Cartilage Development and Diseases by Transcription Factors2017

    • Author(s)
      Nishimura Riko、Hata Kenji、Takahata Yoshifumi、Murakami Tomohiko、Nakamura Eriko、Yagi Hiroko
    • Journal Title

      J Bone Metab

      Volume: 24 Issue: 3 Pages: 147-147

    • DOI

      10.11005/jbm.2017.24.3.147

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptional network controlling endochondral ossification2017

    • Author(s)
      Hata K, Takahata Y, Murakami T, Nishimura R
    • Journal Title

      J Bone Metab

      Volume: 24 Issue: 2 Pages: 75-82

    • DOI

      10.11005/jbm.2017.24.2.75

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Identification of Chondrocyte-specific Sox9 Enhancers Important for Skeletal Development2021

    • Author(s)
      Kobayashi S, Hata K, Takahata Y, Murakami T, Uzawa N, Nishimura R.
    • Organizer
      ASBMR 2021 Annual Meeting(
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 軟骨細胞におけるSox9遺伝子のエンハンサー領域の同定と機能解析2021

    • Author(s)
      小林 紗知, 波多 賢二, 高畑 佳史,村上 智彦,西村 理行
    • Organizer
      第39回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Dmrt2 promotes transition of endochondral ossification by linking Sox9 and Runx22021

    • Author(s)
      Hata K, Ono K, Nakamura E, Kobayashi S, Takahata Y, Murakami T, Nishimura R
    • Organizer
      48th annual meeting of the European Calcified Tissue Society(
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of bone and cartilage development by transcription factors.2019

    • Author(s)
      Nishimura R.
    • Organizer
      9th Japan-Thai-Korea Dental Symposium.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification and functional analysis of novel target genes regulated by Runx2.2019

    • Author(s)
      Takahata Yoshifumi, Wakamori Kanta, Fujiwara Chica, Nakamura Eriko, Hata Kenji, Murakami Tomohiko, Nishimura Riko
    • Organizer
      IFMRS 3rd Herbert Fleisch Workshop
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 転写制御と骨格系疾患の分子機構2018

    • Author(s)
      波多 賢二、村上 智彦、高畑 佳史、西村 理行
    • Organizer
      第60回 歯科基礎医学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Role of transcription factors in cartilage development and diseases2018

    • Author(s)
      Nishimura Riko
    • Organizer
      15th Bone Biology Forum
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 内軟骨性骨形成過程における転写因子の役割2018

    • Author(s)
      西村 理行
    • Organizer
      第36回日本骨代謝学会学術集会学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regulation of endochondral ossification by transcriptopn factors and diseases2017

    • Author(s)
      Riko Nishimura
    • Organizer
      5th Seoul Symposium on Bone Health & 29th Spring Scientific Congress of Korean Society for Bone and Mineral Research
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 関節軟骨の生体恒常性の維持および破綻機構の統合的理解に基づく革新的医療技術の開発2017

    • Author(s)
      西村 理行
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Book] Cell-to-Cell Communication; Cell Atlas; Visual Biology in Oral Medicine2022

    • Author(s)
      Riko Nishimura and Hendrik Terheyden
    • Publisher
      Quintessence Publishing Deutschland
    • Related Report
      2020 Annual Research Report

URL: 

Published: 2016-06-01   Modified: 2023-10-16  

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