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Development and application of the control methods against alveolar bone resorption using human monoclonal antibody

Research Project

Project/Area Number 13557192
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Periodontal dentistry
Research InstitutionKyushu Dental College

Principal Investigator

NISHIHARA Tatsuji  Kyushu Dental College Department of Oral Microbiology Professor, 歯学部, 教授 (80192251)

Co-Investigator(Kenkyū-buntansha) TOMINAGA Akihiro  Seikagaku Corporation Tokyo Research Institute Manager, 中央研究所, 研究員 (60135530)
KAWAHARA Hiroharu  Kitakyushu National College of Technology Department of Material Science and Chemical Engineering Assistant Professor, 生物化学工業, 助教授 (20321515)
TUJISAWA Toshiyuki  Kyushu Dental College Department of Oral Microbiology Assistant, 歯学部, 助手 (60265006)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 2002: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2001: ¥5,800,000 (Direct Cost: ¥5,800,000)
Keywordshuman monoclonal antibody / periodontitis / inflammatory bone resorption / inflammatory cytokine / RANKL / osteoclast / electroporation / alveolar bone resorption / 炎症性骨吸収 / 歯周病 / 炎症性サイトカイン / インターロイキン-1
Research Abstract

Osteoclasts, bone resorbing multinucleated cells, develop from monocyte-macrophage lineage cells in the presence of receptor activator NF-kB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). M-CSF-dependent bone marrow macrophages from mouse bone marrow cells have been shown to differentiate into osteoclast-like multinucleated cells (OCLs) in the presence of soluble RANKL and M-CSF. To investigate human biological responses, it is better to use human-derived proteins, such as human recombinant proteins and monoclonal antibodies. In the present study, we established human hybridomas secreting antibodies against RANKL using in vivo immunization of peripheral blood lymphocytes, and obtained some positive clones. We found that human anti-RANKL monoclonal antibody partially suppress the formation of OCL in vitro. Next, we tried to establish a method of in vivo electroporation to control the inflammatory bone resorption using human anti-RANKL antibody. However, we have no positive results in this study. Further work is needed to put a human monoclonal antibody against RANKL to practical use. Taken together, these results suggest that human monoclonal antibody against RANKL may be useful to control the inflammatory bone resorption in periodontitis.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Hashimoto et al.: "Intracellular apoptosis-inducing factor is induced by a vacuolar type H+-ATPase inhibitor in B lineage cells"J Cellular Physiology. 186. 65-72 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okahashi et al.: "Involvement of cycline-dependent kinase inhibitors p21 and p27 in the differentiation of osteoclasts"J Cellular Biochemistry. 80. 339-345 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishihara et al.: "Effect of aging on interleukin-6 release for human gingival fibroblasts stimulated with in terleukin-1B"Dentistry in Japan. 37. 20-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakashima et al.: "Nitric oxide-mediated protection of A.actinomycetemcomitans-induced murine macrophages against apoptosis"Nitric Oxide : Biology and Chemistry. 6. 61-68 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aiko et al.: "Involvement of cytochrome c and caspases in apoptotic cell death of human submandibular gland ductal cells induced by concanamycin A"Cellular Signalling. 14. 717-722 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamato et al.: "Activation of the p21 promoter by morphogenetic protein 2 in mouse B lineage cells"Oncogene. (Accepted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hashimoto, S., A.Ishisaki, K.Yamato, K.Aiko, T.Amagasa, and T.Nishihara: "Intracellular apoptosis-inducing factor is induced by a vacuolar type H^+-ATPase inhibitor in B lineage cells"J.Cell.Physiol.. 186. 65-72 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nonaka, K., A.Ishisaki, N.Okahashi, T.Koseki, S.Kato, M.Muro, K.Nakashima, T.Nishihara, and Y.Kowashi: "Involvement of caspases in apoptotic cell death of macrophages infected with Actinobacillus actinomycetemcomitans"J.Periodont.Res.. 36. 40-47 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okahashi, N., Y.Murase, T.Koseki, T.Sato, K.Yamato, and T.Nishihara: "Involvement of cyclin-dependent kinase inhibitors P21^<WAF1/CIP1> and p27^<KIP1> in the differentiation of osteoclasts"J.Cell.Biochem.. 80. 339-345 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishihara, T., O.Kawai, K.Nakashima, M.Mori, S.Kato, and Y.Kowashi: "Effect of aging on interteukin-6 release from human gingival fibroblasts with interleukin-1β"Dentistry in Japan. 37. 20-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuchi, Y., M.Kizaki, K.Yamato, C.Kawamura, A.Umezawa, J.Hata, T.Nishihara, and Y.Ikeda: "Mcl-1, an early-induction molecule, modulates activin A-induced apoptosis and differentiation of CML cells"Oncogene. 20. 704-713 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saiki, K., K.Konishi, T.Gomi, T.Nishihara, and M.Yoshikawa: "Reconstitution and purification of cytolethal distending toxin of Actinobacillus actinomycetemcomitans"Microbiol.Immunol.. 45. 497-506 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murase, Y., N.Okahashi, T.Koseki, K.Itoh, N.Udagawa, O.Hashimoto, H.Sugino, T.Noguchi, and T.Nishihara: "Possible involvement of protein kinases and Smad2 signaling pathways on osteoclast differentiation enhanced by activin A"J.Cell.Physiol.. 188. 236-242 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koseki, T., Y.Gao, N.Okahashi, Y.Murase, T.Tsujisawa, T.Sato, K.Yamato, and T.Nishihara: "Role of TGF-β family in osteoclastogenesis induced by RANKL"Cell Signal. 14. 31-36 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato, T., T.Koseki, K.Yamato, K.Saiki, K.Konishi, M.Yoshikawa, I.Ishikawa, and T.Nishihara: "p53-independent expression of P21^<WAF1/CIP1> in plasmacytic cells during G2 cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin"Infect.Immun.. 70. 528-534 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakashima, K., J.Tomioka, S.Kato, T.Nishihara and Y.Kowashi: "Nitric oxide-mediated protection of A. actinomycetemcomitans-infected murine macrophages against Apoptosis"Nitric Oxide : Biology and Chemistry. 6. 61-68 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aiko, K., T.Tsujisawa, T.Koseki, S.Hashimoto, Y.Morimoto, T.Amagasa, and T.Nishihara: "Involvement of cytochrome c and caspases in apoptotic cell death of human submandibular gland ductal cells induced by concanamycin A"Cell Signal. 14. 717-722 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li, X., N.Udagawa, K.Itoh, K.Suda, Y.Murase, T.Nishihara, T.Suda, and N.Takahashi: "p38 MAPK-mediated signals are required for inducing osteoclast differentiation but not for osteoclast function"Endocrinology. 143. 3105-3113 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakahara, T., K.Tominaga, T.Koseki, M.Yamamoto, K.Yamato, J.Fukuda, and T.Nishihara: "Growth/differentiation factor-5 induces growth arrest and apoptosis in mouse B lineage cells with modulation by Smad"Cell Signal. 15. 181-187 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitamura, C., Y.Ogawa, T.Nishihara, T.Morotomi, and M.Terashita: "Transient colocalization of c-Jun N-terminal kinase and c-Jun with heat shock protein 70 in pulp cells during apoptosis"J.Dent.Res.. Accepted. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakashima, K., J.Tanioka, et al.: "Nitric Oxide-mediated protection of A. actinomycetemcomitans-infected murine macrophages against apoptosis"Nitric Oxide : Biology and Chemistry. 6. 61-68 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aiko, K., T.Tsujisawa et al.: "Involvement of cytochrome c and caspases in apoptotic cell death of human submandibular gland ductal cells induced by concanamycin A"Cellular Signalling. 14. 717-722 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamato, K., S.Hashimoto et al.: "Activation of the p21 promoter by morphogenetic protein-2 in mouse B lineage cells"Oncogene. (Accepted).

    • Related Report
      2002 Annual Research Report
  • [Publications] Hashimoto et al.: "Intracellular apoptosis-inducing factor is induced by a vacuolar type H^+-ATPase inhibitor in B lineage cells"J Cell Physiol. 186. 65-72 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okahashi et al.: "Involvement of cyclin-dependent kinase inhibitors p21 and p27 in the differentiation of osteoclasts"J Cell Biochem. 80. 339-345 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishihara et al.: "Effect of aging on interleukin-6 release from human ginziual fibroblasts stimulated with interleukin-1B"Dentistry in Japan. 37. 20-25 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukuchi et al.: "Mcl-1, an early-induction molecule, modulates activin A-induced apoptosis and differentiation of CML cells"Oncogene. 20. 704-713 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koseki et al.: "Role of TGF-B family in osteoclastogenesis induced by RANKL"Cell Signal. 14. 31-36 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sato et al.: "p53-independent expression of p21 in plasmacytic cells during G2 cell cycle arrest induced by Actinobacillus actinomycetem comitans"Infect Immun. 70. 528-534 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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