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Regulation of bone metabolism by alternative splicing during osteoclast differentiation.

Research Project

Project/Area Number 18K09053
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionTokyo University of Science

Principal Investigator

Hayata Tadayoshi  東京理科大学, 薬学部生命創薬科学科, 准教授 (40420252)

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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords破骨細胞 / RNA結合タンパク質 / 核内構造体 / 骨粗鬆症 / 関節リウマチ / 選択的スプライシング / 骨代謝 / 骨疾患
Outline of Final Research Achievements

We investigated the role of the RNA-binding protein Cpeb4 gene during osteoclast differentiation Cpeb4 gene expression was elevated during osteoclast differentiation, and the Cpeb4 protein was localized to the nuclear bodies via the PI3K / Akt signaling and the Nfatc1 activation pathway in a RANKL-dependent manner. Cpeb4 co-localized and interacted with the splicing factor in the nucleus. Osteoclast differentiation was inhibited in cells in which Cpeb4 was knocked down, and the expression of osteoclast differentiation-related genes was significantly reduced revealed by RNA-seq analysis. our results suggest that Cpeb4 is an RNA-binding protein essential for osteoclast differentiation, localizes to the nuclear structure in a RANKL-dependent manner, and may be involved in splicing events.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は,骨や関節の病気における病態解明や、より効果的な治療薬の開発につながる可能性があり、ひいては今後の超高齢化社会における生活の質(QOL)の向上に寄与すると期待される。Cpeb4が破骨細胞分化を促進する詳細なメカニズムが今後さらに明らかになれば、骨粗鬆症や関節リウマチなどの骨や関節の病気の病態の解明につながり、さらにはこれらの病気に対する治療薬の開発が期待される。特に骨粗鬆症に悩む高齢者にとってQOLの向上につながる可能性があるのではないかと考えられる。

Report

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

    (43 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (29 results) (of which Int'l Joint Research: 10 results,  Invited: 2 results) Remarks (2 results)

  • [Int'l Joint Research] Max Planck Institute of Biochemistry(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Valencia(スペイン)

    • Related Report
      2018 Research-status Report
  • [Journal Article] The RNA-binding protein Cpeb4 is a novel positive regulator of osteoclast differentiation2020

    • Author(s)
      Arasaki Yasuhiro、Li Masamichi、Akiya Takuro、Nozawa Iori、Ezura Yoichi、Hayata Tadayoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 528 Issue: 4 Pages: 621-627

    • DOI

      10.1016/j.bbrc.2020.05.089

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of two human induced pluripotent stem cell lines derived from two juvenile nephronophthisis patients with NPHP1 deletion2020

    • Author(s)
      Arai Yutaka、Takami Miho、An Yuri、Matsuo-Takasaki Mami、Hemmi Yasuko、Wakabayashi Tamami、Inoue Jun、Noguchi Michiya、Nakamura Yukio、Sugimoto Keisuke、Takemura Tsukasa、Okita Keisuke、Osafune Kenji、Takasato Minoru、Hayata Tadayoshi、Hayashi Yohei
    • Journal Title

      Stem Cell Research

      Volume: 45 Pages: 101815-101815

    • DOI

      10.1016/j.scr.2020.101815

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RNA結合タンパク質による破骨細胞分化制御2020

    • Author(s)
      荒崎恭弘,李政道,秋谷拓郎,野澤伊織,早田匡芳
    • Journal Title

      Bio Clinica

      Volume: 35 Pages: 53-55

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 骨格形成とTGF-β制御因子2019

    • Author(s)
      早田匡芳,村地眸,荒崎恭弘,秋谷拓郎
    • Journal Title

      Bio Clinica

      Volume: 34 Pages: 48-52

    • Related Report
      2019 Research-status Report
  • [Journal Article] TGF-β抑制因子Dullard/Ctdnep1による骨格制御2019

    • Author(s)
      早田匡芳,野澤伊織,村地眸,秋谷拓郎,荒崎恭弘
    • Journal Title

      Precision Medicine

      Volume: 2 Pages: 52-56

    • Related Report
      2019 Research-status Report
  • [Journal Article] Cyclic stretch induces decorin expression via yes-associated protein in tenocytes: A possible mechanism for hyperplasia in masticatory muscle tendon-aponeurosis hyperplasia2019

    • Author(s)
      Hayashi Naoki、Sato Tsuyoshi、Yumoto Megumi、Kokabu Shoichiro、Fukushima Yosuke、Kawata Yumiko、Kajihara Takeshi、Mizuno Yumi、Mizuno Yosuke、Kawakami Tetsuji、Kirita Tadaaki、Hayata Tadayoshi、Noda Masaki、Yoda Tetsuya
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

      Volume: ― Issue: 3 Pages: 175-179

    • DOI

      10.1016/j.ajoms.2018.12.012

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Profilin 1 Negatively Regulates Osteoclast Migration in Postnatal Skeletal Growth, Remodeling, and Homeostasis in Mice2019

    • Author(s)
      Shirakawa Jumpei、Kajikawa Shuhei、Bottcher Ralph T、Costell Mercedes、Izu Yayoi、Hayata Tadayoshi、Noda Masaki、Ezura Yoichi
    • Journal Title

      JBMR Plus

      Volume: ― Issue: 6

    • DOI

      10.1002/jbm4.10130

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Possible association of oestrogen and Cryba4 with masticatory muscle tendon-aponeurosis hyperplasia2018

    • Author(s)
      Hayashi Naoki、Sato Tsuyoshi、Kokabu Shoichiro、Usui Michihiko、Yumoto Megumi、Ikami Eiji、Sakamoto Yasushi、Nifuji Akira、Hayata Tadayoshi、Noda Masaki、Yoda Tetsuya
    • Journal Title

      Oral Diseases

      Volume: 印刷中 Issue: 1 Pages: 274-281

    • DOI

      10.1111/odi.12876

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dok-3 and Dok-1/-2 adaptors play distinctive roles in cell fusion and proliferation during osteoclastogenesis and cooperatively protect mice from osteopenia2018

    • Author(s)
      Kajikawa Shuhei、Taguchi Yuu、Hayata Tadayoshi、Ezura Yoichi、Ueta Ryo、Arimura Sumimasa、Inoue Jun-ichiro、Noda Masaki、Yamanashi Yuji
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 498 Issue: 4 Pages: 967-974

    • DOI

      10.1016/j.bbrc.2018.03.090

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dullard deficiency causes hemorrhage in the adult ovarian follicles2018

    • Author(s)
      Hayata Tadayoshi、Chiga Masahiko、Ezura Yoichi、Asashima Makoto、Katabuchi Hidetaka、Nishinakamura Ryuichi、Noda Masaki
    • Journal Title

      Genes to Cells

      Volume: 23 Issue: 5 Pages: 345

    • DOI

      10.1111/gtc.12575

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Post-transcriptional regulation of bone metabolism2020

    • Author(s)
      Hayata T
    • Organizer
      7th Lithuania-Japan Joint Life Sciences Symposium
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dullard/Ctdnep1 negatively regulates Smad2/3 protein level and TGF-β signaling in osteoblastic cells2020

    • Author(s)
      Nozawa I, Arasaki Y, Akiya T, Inui M, Noda M, Ezura Y, Hayata T
    • Organizer
      American Society for Bone Mineral and Research annual meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Gprc5a is a novel target gene of teriparatide involved in osteoblastic cell proliferation.2020

    • Author(s)
      Kato K, Arasaki Y, Akiya T, Noda M, Ezura Y, Hayata T
    • Organizer
      American Society for Bone Mineral and Research annual meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RNA-binding protein Cpeb4 is required for osteoclastogenesis2020

    • Author(s)
      Li M, Arasaki Y, Akiya T, Nozawa I, Ezura Y, Hayata T
    • Organizer
      American Society for Bone Mineral and Research annual meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RNA-binding Protein Cpeb4 Is Localized in Nuclei duringOsteoclast Differentiation2020

    • Author(s)
      Arasaki Y, Li M, Akiya T, Nozawa I, Ezura Y, Hayata T
    • Organizer
      American Society for Bone Mineral and Research annual meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RNA結合タンパク質Cpeb4は破骨細胞分化過程で核内局在する2020

    • Author(s)
      荒崎 恭弘,李 政道,秋谷 拓郎,野澤 伊織,江面 陽一 ,早田 匡芳
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] RNA結合タンパク質Cpeb4は破骨細胞形成に必要な因子である2020

    • Author(s)
      李 政道,荒崎 恭弘,秋谷 拓郎,野澤 伊織,江面 陽一 ,早田 匡芳
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] テリパラチドの骨形成促進作用におけるGprc5aの機能解明2020

    • Author(s)
      加藤 宏典,野田 政樹,江面 陽一,早田 匡芳
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] RNA結合タンパク質Cpeb4は破骨細胞分化過程で核内局在する2020

    • Author(s)
      荒崎 恭弘,李 政道,江面 陽一,早田 匡芳
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] RNA結合タンパク質Cpeb4による破骨細胞分化制御機構の解明2020

    • Author(s)
      李 政道,荒崎 恭弘,江面 陽一,早田 匡芳
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] RNA結合タンパク質Cpeb4は破骨細胞分化を正に制御する2020

    • Author(s)
      李 政道,荒崎 恭弘,秋谷 拓郎,野澤 伊織,江面 陽一,早田 匡芳
    • Organizer
      第64回日本薬学会関東支部大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] RNA結合タンパク質Cpeb4は破骨細胞分化過程で核内局在する2020

    • Author(s)
      荒崎 恭弘,李 政道,秋谷 拓郎,野澤 伊織,江面 陽一,早田 匡芳
    • Organizer
      第64回日本薬学会関東支部大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] テリパラチドの骨形成促進作用におけるGprc5aの機能解明2020

    • Author(s)
      加藤 宏典,荒崎 恭弘,秋谷 拓郎,野田 政樹,江面 陽一,早田 匡芳
    • Organizer
      第64回日本薬学会関東支部大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脱リン酸化酵素DullardはSMAD2/3タンパク質レベルを減少させる2020

    • Author(s)
      野澤 伊織,荒崎 恭弘,秋谷 拓郎,乾 雅史,野田 政樹,江面 陽一,早田 匡芳
    • Organizer
      第64回日本薬学会関東支部大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 破骨細胞分化誘導因子RANKLによるCpeb4核内局在機構の解明2019

    • Author(s)
      荒崎 恭弘,秋谷 拓郎,早田 匡芳
    • Organizer
      第6回JCRベーシックリサーチカンファレンス
    • Related Report
      2019 Research-status Report
  • [Presentation] 破骨細胞分化過程におけるRANK mRNA安定性制御機構の解析2019

    • Author(s)
      秋谷 拓郎,荒崎 恭弘,早田 匡芳
    • Organizer
      第6回JCRベーシックリサーチカンファレンス
    • Related Report
      2019 Research-status Report
  • [Presentation] 破骨細胞分化誘導因子RANKLによるCpeb4核内局在機構の解明2019

    • Author(s)
      荒崎 恭弘,秋谷 拓郎,早田 匡芳
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 破骨細胞分化過程におけるRANK mRNA安定性制御機構の解析2019

    • Author(s)
      秋谷 拓郎,荒崎 恭弘,早田 匡芳
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Col1a1-Cre targets the ovary and testis.2019

    • Author(s)
      Hayata T, Ezura Y, Asashima M, Nishinakamura R, Noda M
    • Organizer
      American Society for Bone Mineral and Research annual meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Diverse physiological functions of the TGF-β/BMP signaling suppressor Dullard/Ctdnep1.2019

    • Author(s)
      Hayata T
    • Organizer
      6th Lithuania-Japan Joint Life Sciences Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Col1a1-Creは、卵巣と精巣を標的とする2019

    • Author(s)
      早田匡芳、江面陽一、野田政樹
    • Organizer
      第37回日本骨代謝学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] TGF-β/BMPシグナル抑制分子Dullard/Ctdnep1の多彩な生理機能2018

    • Author(s)
      早田 匡芳
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] he ovarian hemorrhages caused by the phosphatase Dullard deficiency is rescued by administration of a BMP type I receptor kinase inhibitor.2018

    • Author(s)
      Hayata T, Chiga M, Ezura Y, Asashima M, Katabuchi H, Nishinakamura R, Noda M.
    • Organizer
      12th International BMP conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Profilin1 deficiency in osteoclasts causes osteolytic developmental bone deformities due to increased osteoclast movements and differentiation.2018

    • Author(s)
      Kajikawa S, Shirakawa J, Hayata T, Izu Y, Bottcher RT, Costell M, Noda M, Eura Y.
    • Organizer
      28th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Profilin1 negatively regulates osteoclast migration in postnatal skeletal growth and remodeling in mice.2018

    • Author(s)
      Kajikawa S, Shirakawa J, Hayata T, Izu Y, Bottcher RT, Costell M, Noda M, Eura Y.
    • Organizer
      15th Bone Biology Forum
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 骨形成制御に関わるcAMP径路の標的分子と下流バランス2018

    • Author(s)
      江面 陽一、梶川 修平、勝村 早恵、白川 純平、早田 匡芳、野田 政樹
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] アクチン重合を制御するプロフィリン1欠損破骨細胞は遊走・分化・骨吸収を亢進させ、マウスの溶骨症性骨変形を生じる。2018

    • Author(s)
      江面 陽一、白川 純平、梶川 修平、伊豆 弥生、早田 匡芳、Bottcher RT、Costel M、野田政樹
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] アクチン重合の制御因子プロフィリン1 を欠損するマウス破骨細胞は遊走・分化・骨吸収の亢進により溶骨症性骨変形を生じさせる。2018

    • Author(s)
      梶川 修平、白川 純平、早田 匡芳、伊豆 弥生、ベッチャー ラルフ、野田 政樹、江面 陽一
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] アダプター分子 Dok-3 と Dok-1/-2 は互いに異なる様式で骨形成を促進し、個体の骨量維持に必須の役割を果たす。2018

    • Author(s)
      植田 亮、梶川 修平、田口 祐、早田 匡芳、江面 陽一 、有村 純暢、井上 純一郎、野田 政樹、山梨 裕司
    • Organizer
      第18回東京大学生命科学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Remarks] 東京理科大学 大学院薬学研究科・薬学部 分子薬理学研究室

    • URL

      https://sites.google.com/view/thehayatalab/home

    • Related Report
      2020 Annual Research Report
  • [Remarks] 東京理科大学 薬学部 分子薬理学

    • URL

      https://sites.google.com/view/thehayatalab/home

    • Related Report
      2019 Research-status Report 2018 Research-status Report

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

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