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Establishment of Bone Metabolism Research through Regulation of Osteoclast Differentiation and Functions

Research Project

Project/Area Number 15591947
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SASAKI Takahisa  Showa University, School of Dentistry, Professor, 歯学部, 教授 (50129839)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Naoyuki  Matsumoto Dental University, Institute for Dental Science, Professor, 総合歯科医学研究所, 教授 (90119222)
伊藤 雅波  昭和大学, 歯学部, 助手 (10349045)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsin vitro / in vivo / RANKL / OPG / H-ATPase / cathepsin K / osteoclast / osteoporosis / 骨吸収
Research Abstract

We conducted in vitro and in vivo experiments to clarify the biological effects of receptor activator of NFkB ligand (RANKL) and osteoprotegerin (OPG). We also examined the effects of potent and specific inhibitors for H-ATPase and cathepsin K in osteoclasts. The main methods we conducted were (1) cultures of osteoclast precursors and mature osteoclasts, (2) quantitative morphometry of resorption lacunae formed on co-cultured dentine slices, (3) ultrastructural observations of osteoclasts, (4) immunohistochemistry of H-ATPase and cathepsin K in osteoclasts, (5) scanning electron microscopic observations of resorption lacunae and associated osteoclasts. In this project, we examined specific biological effects of these cytokines and inhibitors for differentiation of osteoclast precursors. We also examined specific biological effects of these cytokines and inhibitors for cell structure, survival time, resorptive functions of mature osteoclasts. In addition, we cultured osteoclast precursors on the slices of calcified bone, decalcified bone, or uncalcified cartilage and found that osteoclast differetiation and functions were different depend on these substrata. In our in vivo experiments, we conducted morphometric and immunocytochemical examinations to clarify the effects of bisphosphonate or OPG on osteoclast differentiation and functional structures to inhibit acute bone loss in estrogen-deficient osteoporosis animal models. All the results obtained suggest that regulation of osteoclast differentiation is effective biological tool to normalize bone metabolism in various metabolic bone diseases.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (17 results)

All 2004 2003 Other

All Journal Article (9 results) Book (2 results) Publications (6 results)

  • [Journal Article] Specific biological functions of vacuolar-typeH-ATPase and lysosomal cysteine proteinease, cathepsin K, in osteoclasts.2003

    • Author(s)
      Sahara T, Itoh k, Debari K, Sasaki T
    • Journal Title

      Anatomical Record 270A

      Pages: 152-161

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Involvement of H-ATPase in incroporation of rsedronate into osteoclasts.2003

    • Author(s)
      Takami M, Sahara T, Sasaki T et al.
    • Journal Title

      Bone 32

      Pages: 341-349

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Destruxins, cyclodepsipeptides, block the formation of actin rings and prominent clear zones and ruffled borders in osteoclasts.2003

    • Author(s)
      Nakagawa H, Takami M, Udagawa N, Sawae Y, Suda K, Sasaki T et al.
    • Journal Title

      Bone 33

      Pages: 443-455

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Cellular mechanisms of inhibition of osteoclastic resorption of bone and calcified cartilage by long-term pamidronate administration in OVX mature rats.2003

    • Author(s)
      Mayahara M, Sasaki T
    • Journal Title

      Anatomical Record 274A

      Pages: 817-826

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Osteoclast differentiation at growth plate cartilage -tabecular bone junction in newbone rat femur.2003

    • Author(s)
      Sawae Y, Sahara T, Sasaki T
    • Journal Title

      Journal of Electron Microscopy 52(6)

      Pages: 493-502

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Osteoclast differentiation and characteristic trabecular bone formation during growth plate destruction in osteoprotegerin-deficient mice.2003

    • Author(s)
      Kawana F, Sasaki T
    • Journal Title

      Journal of Electron Microscopy 52(6)

      Pages: 515-525

    • NAID

      10011950833

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Specific biological functions of vacuolar-typeH-ATPase and lysosomal cysteine proteinease, cathepsin K, in osteoclasts.2003

    • Author(s)
      Sahara T, Itoh k, Debari k, Sasaki T
    • Journal Title

      Anatomical Record 270A

      Pages: 152-161

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differentiation and functions of osteoclasts and odontoclasts in mineralized tissue resorption.2003

    • Author(s)
      Sasaki T
    • Journal Title

      Microscopy Research and Technique 61

      Pages: 483-495

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Specific biological functions of vacuolar-typeH-ATPase and lysosomal cysteine proteinease cathepsin K in osteoclasts.2003

    • Author(s)
      Sahara T, Itoh k, Debari k, Sasaki T
    • Journal Title

      Anatomical Record 270A

      Pages: 152-161

    • Related Report
      2004 Annual Research Report
  • [Book] Biological Mechanisms of Tooth Movement and Craniofacial Adaptation.2004

    • Author(s)
      Mayahara M, Kenmotsu S, Sasaki T
    • Total Pages
      387
    • Publisher
      Amarin Printing and Publishing Public Co.Ltd.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Book] Biological Mechanisms of Tooth Movement and Craniofacial Adaptation2004

    • Author(s)
      Mayahara M, Kenmotsu S, Sasaki T
    • Publisher
      Amarin Printing and Publishing Public Co.Ltd.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Sahara T, Itoh K, Debari K, Sasaki T: "Specific biological functions of vacuolar-typeH-ATPase and lysosomal cysteine proteinease, cathepsin K, in osteoclasts"Anatomical Record. 270A. 152-161 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takami M, Sahara T, Sasaki T et al.: "Involvement of H-ATPase in incroporation of rsedronate into osteoclasts"Bone. 32. 341-349 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mayahara M, Sasaki T: "Cellular mechanisms of inhibition of osteoclastic resorption of bone and calcified cartilage by long-term pamidronate administration in ovariectomized mature rats"Anatomical Record. 274A. 817-826 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakagawa H, Takami M, Udagawa N, Sawae Y, Suda K, Sasaki T et al.: "Destruxins, cyclodepsipeptides, block the formation of actin rings and prominent clear zones and ruffled borders in osteoclasts"Bone. 33. 443-455 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sawae Y, Sahara T, Sasaki T: "Osteoclast differentiation at growth plate cartilage-tabecular bone junction in newbone rat femur"Journal of Electron Microscopy. 52(6). 493-502 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawana F, Sasaki T: "Osteoclast differentiation and characteristic trabecular bone formation during growth plate destruction in osteoprotegerin-deficient mice"Journal of Electron Microscopy. 52(6). 515-525 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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