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APOPTOSIS OF OSTEOCLASTS AND INFLAMMATORY BONE

Research Project

Project/Area Number 10557203
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Periodontal 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, 主任研究官 (40150180)

Co-Investigator(Kenkyū-buntansha) SHIBASAKI Kenichiro  LION Co., Ltd., ORAL CARE RESEARCH INSTITUTE, SENIOR RESEARCHER, オーラルケア研究所, 主任研究員
NISHIHARA Tatsuji  NATIONAL INSTITUTE OF INFECTIOUS DISEASES, DEPARTMENT OF ORAL SCIENCE, CHIEF, 口腔科学部, 室長 (80192251)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥3,100,000 (Direct Cost: ¥3,100,000)
KeywordsOSTEOCLAST / APOPTOSIS / PERIODONTITIS / LIPOPOLYSACCHARIDE / リポ多糖 / サイトカイン
Research Abstract

Periodontitis often results in tooth loss due to inflammatory bone resorption. Bone resorption is mediated by osteoclasts. Although the differentiation pathway of osteoclasts is not well known at present, various inflammatory mediators are known to trigger the production of osteoclasts. We have found that lipopolysaccharides (LPS) of various periodontophatic bacteria mediate osteoclast formation and stimulate bone resorption in vitro. In this project, we investigate the mechanism of osteoclast differentiation mediated by LPS from a periodontophatic bacteria Actinobacillus actinomycetemcomitans.
In mouse bone marrow cultures, LPS of A. actinomycetemocomitans induced osteoclast formation. Indomethacin and anti-IL-1 antibodies significantly inhibited the osteoclast formation, suggesting that prostaglandin E2 (PGE2) and IL-1 were involved in LPS-mediated osteoclast formation. We also found that LPS from A. actinomycetemcomitans induced expression of osteoclast differentiation factor (ODF) on cells of osteoblastic lineage. These results indicated that LPS of A. actinomycetemcomitans mediated osteoclast formation through upregulation of PGE2, IL-1 and ODF in periodontal tissues. Furthermore, we found that taurine, a sulfer containing amino acid, inhibited the osteoclast formation mediated by LPS from A. actinomycetemcomitans. Taurine was also found to inhibit the experimental bone resorption in ligature-mediated periodontitis in hamsters.

Report

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

    (31 results)

All Other

All Publications (31 results)

  • [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(和文)」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(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 osteoclast 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] Yamamoto, S., et al.: "Anti-prolifetative capsular-like polysaccharide antigen from Actinobacillus actinomycetemcomitans induces apoptotic cell death in mouse oseteoblastic MC3T3-E1 cells"J. Dent. Res.. 78. 1230-1237 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Muro, M., et al.: "Inhibitory effect of lipopolysaccharide on apoptotic cell death in macrophages infected with Actinobacillus actinomycetemcomitans"FEMS Microbiol. Lett.. 175. 211-216 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishisaki, A. ,et al.: "Differential Inhibition of Smad6 and Smad7 on bone morphogenetic protein-and activinmediated growth arrest and apoptosis in B cells"J. Biol . Chem.. 274. 13637-13642 (199)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] "1"

    • 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 as 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] Yamamoto, S., et al.,: "Anti-proliferative capsular-like polysaccharide antigen from Actinobacillus actinomycetemcomitans induces apoptotic cell death in mouse osteoblastic MC3T3-E1 cells."J. Dent. Res.. 78. 1230-1237 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Muro, M., et al.,: "Inhibitory effect of lipopolysaccharide on apoptotic cell death in macrophages infected with Actinobacillus actinomycetemcomitans."FEMS Microbiol. Lett.. 175. 211-216 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishisaki, A., et al.,: "Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin- mediated growth arrest and apoptosis in B cells."J. Biol. Chem.. 274. 13647-13642 (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] Yamamoto S.et al.: "Anti-proliferative capsular-like polysaccharide antigen from Actinobacillus actinomycetemcomitans induces apoptotic cell death in mouse osteoblastic MC3T3-E1 cells"J.Dent.Res.. 78. 1230-1237 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Muro M.et al.: "Inhibitory effect of lipopolysaccharide on apoptotic cell death in macrophages infected with Actinobacillus actinomycetemcomitans"FEMS Microbiol.Lett.. 175. 211-216 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishisaki A.et al.: "Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein-and activinmediated growth arrest and apoptosis in B cells"J.Biol.Chem.. 274. 13637-13642 (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
  • [Publications] Hayasida,H.,et.al.: "The differentiation of clinical isolates of Actinobacillus actinomycetemcomitans by using a insertion sequence ISAa1" Oral Microbiol.Immunol.13. 120-123 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueno,H.,et.al.: "A novel retinoic acid receptor (RAR)-selective antagonist inhibits differentiation and apoptosis of HL-60 cells: Implications of RARa-mediated signals in myeloid leukemic cells" Leukemia Res.22. 517-525 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakashima,K.,et.al.: "Two different antigens of Actinobacillus actinomycetemcomitans recognized by high-responder patients" J.Med.Microbiol.47. 569-575 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Koseki,T.,et.al.: "Correlation between Bci-X expression and B cell hybridoma apoptosis induced by activin A" Cell.Signal.10. 517-521 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nonaka,K.,et.al.: "Possible involvement of protein kinase C in apoptotic cell death of macrophages infected with Actinobacillus actinomycetemcomitans" FEMS Microbiol.Lett.159. 247-254 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishisaki,A.,et.al.: "Smad7 is an activin-inducible inhibitor of activin-induced growth arrest and apoptosis in mouse B cells" J.Biol.Chem.273. 24293-24296 (1998)

    • Related Report
      1998 Annual Research Report

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

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