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INHIBITORS FOR VACUOLAR THPE HィイD1+ィエD1-ATPaseINDUCES APOTOSIS IN OSTEOCLASTS

Research Project

Project/Area Number 10671729
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionNATIONAL INSTITUTE OF INFECTIOUS DISEASES

Principal Investigator

OKAHASHI Nobuo  NATIONAL INSTITUTE OF INFECTIOUS DISEASES, DEPARTMENT OF ORAL SCIENCE SENIOR RESEARCHER, 口腔科学部, 主任研究員 (40150180)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsOSTEOCLAST / APOPTOSIS / PERIODONTITIS / CASPASE / LIPOPOLYSACCHARIDE / CYTOKINE / プロトンATPase
Research Abstract

Osteoclasts are multinucleated bone resorbing giant cells. Osteoclasts resorb bone minerals by acid. Production of acid by osteoclast is controlled by carbonic anhydrase and vacuolar type ATPase. Recently, we found that the inhibitors of vacuolar type ATPase trigger apoptotic cell death of osteoclasts. In this research project, we investigate the cellular mechanism of apoptotic events induced by the ATPase inhibitors.
Purified osteoclasts were prepared from mouse bone marrow cultures. Vacuolar type ATPase inhibitors, concanamycin A and bafilomycin induced cell death of purified osteoclast within 24 h. Hoechst stain and FITC-TUNEL revealed apoptotic features of this cell death of osteoclasts. Measurement of caspase activities revealed that ATPase inhibitors activated caspase-1 and caspase-3 during apoptotic events of osteoclasts. Furthermore, activation of caspase-8 and caspase-9 also detected. Fluorescenece labeling of osteoclastic mitochondorial membrene by MitAlert revealed that the mitochondoria membrane was destroyed by the ATPase inhibitors. These results suggested that vacuolar type ATPase plays an important role in bone resorption as well as survival of osteoclasts.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Koide, M., et al.: "Bone morphogenetic protein-2 enhances osteolast formation mediated by interleukin-1a through upregulation of osteolast differentiation factor and cyclooxygenase-2"Biochem. Biophys. Res. Commun.. 250. 67-102 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koide, M., et al.: "Inhibition of experimental bone resorption and osteolast formation and survival by 2-aminoethansulfonic acid"Arch. Oral Biol.. 44. 711-719 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jimi, E., et al.: "Osteoclast differentiation factor acts as a multifunctional regulator in murine osteolast differentiation and function"J. Immunol.. 163. 434-442 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koide, M. et al.,: "Bone morphogenetic protein-2 enhances osteoclast formation mediated by interleukin-1a through upregulation of osteoclast differentiation factor and cyclooxygenase-2."Biochem. Biophys. Res. Commun.. 250. 97-102 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koide, M. et al.: "Inhibition of experimental bone resorption and osteoclast formation and survival by 2-aminoethanesulfonic acid."Arch. Oral Biol.. 44. 711-719 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jimi, E., et al.,: "Osteoclast differentiation factor acts a s a multifunctional regulator in murine osteoclast differentiation and function."J. Immunol.. 163. 434-442 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koide M.et al.: "Bone morphogenetic protein-2 enhances osteoclast formation mediated by interleukin-1a through upregulation of osteoclast differentiation factor and cyclooxygenase-2"Biochem.Biophys.Res.Commun.. 250. 97-102 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koide M.et al.: "Inhibition of experimental bone resorption and osteoclast formation and survival by 2-aminoethanesulfonic acid"Arch.Oral Biol.. 44. 711-719 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jimi E.et al.: "Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function"J.Immunol.. 163. 434-442 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okahashi,N., et.al.: "Specific inhibitors of vacuolar H-ATPase trigger apoptotic cell death of osteoclasts" J.Bone Miner.Res.12. 1116-1123 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akifusa,S.,et.al.: "Increase in Bcl-2 level promoted by CD40 ligation correlates with inhibition of B cell apoptosis induced by vacuolar type H-ATPase inhibitor" Exp.Cell Res.238. 82-89 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okahashi,N.,et.al.: "Caspases(interleukin-1b converting enzyme family proteases)are involved in the regulation of the survival of osteoclasts" Bone. 23. 33-41 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohguchi,M.,et.al.: "Activin A regulates the production of mature interleukin-1b and interleukin-1 receptor antagonist in human monocytic cells" J.Interferon Cytokine Res.18. 491-498 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohguchi,M.,et.al.: "Actinobacillus actinomycetemcomitans toxin induces both cell cycle arrest in the G2/M phase and apoptosis" Infect.Immun.66. 5980-5987 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueda,N.,et.al.: "Involvement of prostaglandin E2 and interleukin-1a in the differentiation and survival of osteoclasts induced by lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4" J.Periodont.Res.33. 509-516 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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