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軟骨・骨におよぼすFGFとPTHrPの作用(遺伝子組み替えマウスを用いた解析)

Research Project

Project/Area Number 11771109
Research Category

Grant-in-Aid for Encouragement of Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Morphological basic dentistry
Research InstitutionNiigata University

Principal Investigator

網塚 憲生  新潟大学, 歯学部, 助手 (30242431)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywords遺伝子欠損マウス / 副甲状腺ホルモン関連ペプチド / 線維芽細胞増殖因子レセプターIII / 骨芽細胞 / 軟骨 / Gli / 線維芽細胞増殖因子レセプター3 / PTH / PTHrPレセプター / 核小体移行 / alternative translation
Research Abstract

平成12年度の目的として、線維芽細胞増殖因子レセプターtype III(FGFR3)遺伝子欠損マウス、ならびにGli-Krupper familyを構成する転写調節因子であるGli遺伝子の欠損モデルマウスを用いて骨・軟骨形成を検索した【平成12年研究計画1】。また、軟骨の増殖分化に関連する副甲状腺ホルモン関連ペプチド(PTHrP)の核小体移行に関する細胞生物学的検討を加えた【平成12年研究計画2】。その結果、FGFR3マウスでは、軟骨細胞の増殖亢進と軟骨・骨移行部における血管侵入の抑制が認められ、特に、後者は血管内皮増殖因子(VEGF)を介していることを報告した(第22回アメリカ骨代謝学会;Acta,Anat.Nipponica,Amizuka,et al.,2000;Histol.Histopath,Amizuka et al.,2000.)。さらに、Gli3遺伝子欠損マウスでは多趾症・多指症とともに、発達の悪い脛骨が観察された。組織学的に、軟骨内骨化に携わる骨原生細胞が過剰なアポトーシスを生じており、アポトーシス誘導因子として作用するBMP-2を介することが明らかとなった(第22回アメリカ骨代謝学会、第17回日本骨代謝学会、網塚ら)。さらに、PTHrPの核小体移行については、開始メチオニンをコードするAUGコドンばかりでなく下流のCUGコドンからのalternative translationが認められること、またその際に、PTHrPタンパクは核小体に移行することを明らかにした(Biochem.Biophys.Res.Commun.,Amizuka et al.,2000)。以上の研究成果は、本来計画した内容を充分満足しており、そのほとんどが論文に受理中である。また、本研究によって日本骨代謝学会学術賞、歯科基礎医学会学会賞を受賞した。

Report

(2 results)
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Amizuka et al.: "Inefficient function of signal sequence of parathyroid hormone-related peptide(PTHrP) for targeting to the secretory pathway. "Biochem.Biophys.Res.Commun.. 273. 621-629 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Amizuka et al.: "Recent studies on the biological action of parathyroid hormone (PTH)-related peptide (PTHrP) and PTH/PTHrP receptor in cartilage and bone."Histol.Histopath.. 15. 957-970 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Amizuka et al.: "The biological action of parathyroid hormone-related peptide (PTHrP) and fibroblast growth factor receptor3 (FGFR3) on bone and cartilage"Acta.Anatomica Nipponica. 75. 415-425 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sasaki et al: "Localization of alkaline phosphatase and osteopontin during mineralization in developing cartilage of candal vertebrae."Arch.Histol.Cytol.. 63. 271-284 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Watanabe et al: "Cytochemical and ultrastructural examination of apoptotic odontoclasts induced by bisphosphonate administration."Cell & Tissue Res.. 301. 375-387 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 網塚憲生 ら: "副甲状腺ホルモン関連ペプチド遺伝子組み替えマウスの軟骨・骨の異常"医学のあゆみ. 192. 740-746 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Amizuka et al.: "Recent Research Development of Endocrinology"The bipartite action of parathyroid hormone (PTH)-related peptide(PTHrP) mediating by binding PTH/PTHrP receptor and translocation into nucleolus.. 375 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 網塚憲生 ら: "新・分子骨代謝学と骨粗鬆症(副甲状腺ホルモン/副甲状腺ホルモン関連タンパク受容体の機能)"(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Amizuka et al.: "Vitamin D3 differentially regulates parathyroid hormone/parathyroid hormone-related peptide receptor expression in bone and cartilage"Journal of Clinical Investigation. 103(3). 373-381 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Horiuchi K, Amizuka et al.: "Identification and characterization of a novel protein, periostin (OSF-2) with restricted expression to periosteum and periodantal ligament"Journal of Bone and Mineral Research. 14. 1239-1249 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito M, Amizuka N et al.: "Ultrastructural and cytochemical observation of apoptotic osteoclasts induced by bisphosphonate"Bone. 25. 447-452 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Wakita K, Amizuka N. et al.: "Maturation ameloblasts of the procine germ do not express amelogenin"Histochem Cell Biol. 111. 297-303 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Izumi N, Amizuka N. et al.: "Ultrastructural alteration of osteoclasts treated with brefeldin A and wortmanin"Acta. Histo. Cyto. 32(5). 393-405 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Karaplis et al.: "Blomstrand chondrodisplasia caused by a missence mutation in the human parathyroid hormone receptor-1"Endocrinology. 139(12). 5255-5258 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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