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The analyses on bone and cartilage diseases caused by mutations of FGFR3/PTHrP genes

Research Project

Project/Area Number 16390524
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionNiigata University

Principal Investigator

AMIZUKA Norio  Niigata University, Center for Transdisciplinary Research, professor, 超域研究機構, 教授 (30242431)

Co-Investigator(Kenkyū-buntansha) MAEDA Takeyasu  Niigata University, Institute of Medicine and Dentistry, professor, 医歯学系, 教授 (40183941)
OZAWA Hidehiro  Matsumoto Dental University, Graduate School of Oral Medicine, professor, 大学院・歯学独立研究科, 教授 (60018413)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥10,800,000 (Direct Cost: ¥10,800,000)
KeywordsFGFR3 / PTHrP / cartilage / ultrastructure / genetargeted mice / 軟骨細胞 / 遺伝子変異 / VEGF / 致死型軟骨無形成症 / 軟骨内骨化 / アポトーシス
Research Abstract

We conducted the broad analyses on the biological function of fibroblast growth factor receptor type III (FGFR3) and parathyroid hormone-related peptide (PTHrP), by employing gene targeted mice, cells transgenes with mutated PTH/PTHrP receptors and bone metastatic mice with PTHrP-overexpressing tumors. In 2004, we have generated FGFR3^<-/->/PTHrP^<-/-> mice, and examined the skeletal deformities on bone and cartilage. As a results, PTHrP dominantly affected on the chondrocyte proliferation, rather than FGFR3. However, FGFR3 could influence the apoptosis and VEGF expression in chondrocytes after their entry to hypertrophic phenotype. In 2005, we have reported that PTHrP stimulated osteoblastic proliferation and survival in an autocrine/paracrine manner. Also, we provided the strong possibility that proteins of mutated PTH/PTHrP receptors, inducing Jansen type and Blomstrand type chondrodysplasia, would be accumulated in endoplasmic reticulum, and subsequent be leaked into the cytoplasmic region. Therefore, the mutant receptors would not be normally targeted to the cell membranes. In addition, we have morphologically examined the metastastic lesion by PTHrP-overexpressing tumors. Thus, we assessed the skeletal pathological features caused by the mutations and abnormal expression of FGFR3 and/or PTHrP genes.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (27 results)

All 2006 2005 2004

All Journal Article (24 results) Book (3 results)

  • [Journal Article] Histochemical evidences of osteoclastic degradation of extracellular matrix in osteolytic metastasis originating from human lung small carcinoma (SBC-5) cells.2006

    • Author(s)
      Li M, Amizuka N, Takeuchi K, Freitas PHL, Kawano Y, Hoshino M, Oda K, Nozawa-Inoue K, Maeda T
    • Journal Title

      Microsc.Res Tech 69(2)

      Pages: 73-83

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ultra structural images of enamel tufts in human permanent teeth.2005

    • Author(s)
      Amizuka N, et al.
    • Journal Title

      J. Oral Biosci. 47(1)

      Pages: 33-41

    • NAID

      110003163515

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Histological evaluation for "Bone Quality" on two mouse models with different bone remodeling.2005

    • Author(s)
      Amizuka N, et al.
    • Journal Title

      J. Bone Miner. Metab. 23

      Pages: 43-47

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH1-34.2005

    • Author(s)
      Miao D, Amizuka N, et al.
    • Journal Title

      J. Clin. Invest. 115(9)

      Pages: 2402-2411

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] VEGF receptor 1 signaling is essential for osteoclast development and bone marrow formation in colony-stimulating factor 1-deficient mice.2005

    • Author(s)
      Niida S, Amizuka N, et al.
    • Journal Title

      Proc. Nat1. Acad. Sc., U. S. A. 102(39)

      Pages: 14016-14021

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Histochemical evidences of osteoclastic degradation of extra cellular matrix in osteolytic metastasis originating from human lung small carcinoma (SBC-5) cells.2005

    • Author(s)
      Li M, Amizuka N, et al.
    • Journal Title

      Microsc. Res. Tech 69(2)

      Pages: 73-83

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ultrastructural images of enamel tufts in human permanent teeth.2005

    • Author(s)
      Amizuka N, Uchida T, Nozawa-Inoue K, Kawano Y, Suzuki A, Li M, Nasu M, Kojima T, Sakagami N, Ozawa H, Maeda.T
    • Journal Title

      J.Oral Biosci. 47(1)

      Pages: 33-41

    • NAID

      110003163515

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Histological evaluation for "Bone Quality" on two mouse models with different bone remodeling.2005

    • Author(s)
      Amizuka N, Shimomura J, Li M, Nasu M, Ozawa H, Maeda T
    • Journal Title

      J.Bone Miner.Metab. 23

      Pages: 43-47

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH1-34.2005

    • Author(s)
      Miao D, He B, Jiang Y, Kobayashi T, Soroceanu MA, Zhao J, Su H, Tong XK, Amizuka N, Gupta A, Genant HK, Kronenberg HM, Goltzman D, Karaplis AC
    • Journal Title

      J.Clin.Invest. 115(9)

      Pages: 2402-2411

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] VEGF receptor 1 signaling is essential for osteoclast development and bone marrow formation in colony-stimulating factor 1-deficient mice.2005

    • Author(s)
      Niida S, Kondo T, Hiratsuka S, Hayashi S, Amizuka N, Noda T, Ikeda K, Shibuya M
    • Journal Title

      Proc.Natl.Acad.Sci., U.S.A. 102(39)

      Pages: 14016-14021

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ultrastructural images of enamel tufts in human permament teeth.2005

    • Author(s)
      Amizuka N, et al.
    • Journal Title

      J.Oral Biosci. 47(1)

      Pages: 33-41

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Histological evaluation for "Bone Quality" on two mouse models with different bone remodeling.2005

    • Author(s)
      Amizuka N, et al.
    • Journal Title

      J.Bone Miner.Metab. 23

      Pages: 43-47

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Histological observations on the microenvironment of osteolytic bone metastasis by breast carcinoma cell line.2005

    • Author(s)
      Shimamura T, Amizuka N, et al.
    • Journal Title

      Biomed.Res 26(4)

      Pages: 159-172

    • NAID

      130004470647

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH1-34.2005

    • Author(s)
      Miao D, Amizuka N, et al.
    • Journal Title

      J.Clin.Invest. 115(9)

      Pages: 2402-2411

    • Related Report
      2005 Annual Research Report
  • [Journal Article] VEGF receptor 1 signaling is essential for osteoclast development and bone marrow formation in colony-stimulating factor 1-deficient mice.2005

    • Author(s)
      Niida S, Amizuka N, et al.
    • Journal Title

      Proc.Natl.Acad.Sci., U.S.A. 102(39)

      Pages: 14016-14021

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Histochemical evidences of osteoclastic degradation of extracellular matrix in osteolytic metastasis originating from human lung small carcinoma (SBC-5) cells.2005

    • Author(s)
      Li M, Amizuka N, et al.
    • Journal Title

      Microsc.Res.Tech 69(2)

      Pages: 73-83

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Histological evaluation for "Bone Quality" on two mouse models with different bone remodeling2005

    • Author(s)
      N.Amizuka
    • Journal Title

      J Bone Miner Metab. (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Signalling by fibroblast growth factor receptor 3 and parathyroid hormone-related peptide coordinate cartilage and bone development.2004

    • Author(s)
      Amizuka N, et al.
    • Journal Title

      Bone 34

      Pages: 13-25

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Signalling by fibroblast growth factor receptor 3 and parathyroid hormone-related peptide coordinate cartilage and bone development.2004

    • Author(s)
      Amizuka, N., Davidson D, Liu H, Valverde-Franco G, Chai S, Maeda T, Ozawa H, Hammond V, Ornitz DM, Goltzman D, Henderson, JE.
    • Journal Title

      Bone 34

      Pages: 13-25

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A histological evaluation on self-setting alpha-tricalcium phosphate applied in the rat bone cavity.2004

    • Author(s)
      H.Hao
    • Journal Title

      Biomaterials 25

      Pages: 431-442

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Signalling by fibroblast growth factor receptor 3 and parathyroid hormone-related peptide coordinate cartilage and bone development2004

    • Author(s)
      N.Amizuka
    • Journal Title

      Bone 34

      Pages: 13-25

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Zebrafish periostin is required for the adhesion of muscle fiber bundles to myoseptum and the differentiation of muscle fibers.2004

    • Author(s)
      H.Kudo
    • Journal Title

      Develop.Biol. 267

      Pages: 473-487

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Morphological approach to biological action of PTHrP and vitamin D3 on endochondral ossification.2004

    • Author(s)
      N.Amizuka
    • Journal Title

      J.Oral Biosci. 46(2)

      Pages: 79-96

    • NAID

      110003166636

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene expression of periostin in the early stage of fracture healing detected by cDNA microarray analysis.2004

    • Author(s)
      T.Nakazawa
    • Journal Title

      J.Orthop.Res. 22(3)

      Pages: 520-525

    • Related Report
      2004 Annual Research Report
  • [Book] 副甲状腺ホルモン/副甲状腺ホルモン関連ペプチド受容体とシグナル伝達.臨床内分泌学3-甲状腺・副甲状腺・骨内分泌代謝系-2005

    • Author(s)
      網塚憲生, 他
    • Total Pages
      642
    • Publisher
      日本臨牀
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 副甲状腺ホルモン/副甲状腺ホルモン関連ペプチド受容体遺伝子改変マウス.臨床内分泌学3-甲状腺・副甲状腺・骨内分泌代謝系-2005

    • Author(s)
      網塚憲生, 他
    • Total Pages
      642
    • Publisher
      日本臨牀
    • Related Report
      2005 Annual Research Report
  • [Book] -甲状腺・副甲状腺・骨内分泌代謝系-2005

    • Author(s)
      網塚憲生
    • Publisher
      日本臨牀(印刷中)
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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