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Study of odontotherapy rerated-osteonecrosis of the jaw following to long-term bisphosphonate application

Research Project

Project/Area Number 18592162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionHokkaido University

Principal Investigator

DEYAMA Yoshiaki  Hokkaido University, Grad., Sch., Dent Med., Associate Professor (80271667)

Co-Investigator(Kenkyū-buntansha) TOTSUKA Yasunori  Hokkaido University, Grad., Sch., Dent Med., Professor (00109456)
TEI Kanchu  Hokkaido University, Grad., Sch., Dent Med., Asso. Prof. (80180066)
IIZUKA Tadashi  Hokkaido University, Grad., Sch., Dent Med., Associate Professor (80168062)
YOSHLMURA Yoshitaka  Hokkaido University, Grad., Sch., Dent Med., Assistant Professor (30230816)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsbisphosphonate / osteonecrosis / odontotherapy / 顎骨壞死
Research Abstract

Intravenous bisphosphonates are primarily used and effective in the treatment and management of cancer-related conditions. These include hypercalcemia of malignancy, skeletal-related events associated with bone metastases in the context of solid tumors such as breast cancer, prostate cancer, and lung cancer, and in the management of lytic lesions in the setting of multiple myeloma. Oral bisphosphonates are approved to treat osteoporosis and are frequently used to treat osteopenia as well. They are also used for a variety of less common conditions such as Paget's disease of bone, and osteogenesis imperfecta of childhood. Recently, cases of nonhealing exposed, necrotic bone in the maxillofacial region in patients treated with intraveneous bisphosphonates, pamidronate and zoledronic acid, have been recognized and reported. To date, the incidence and pathophysiology of osteonecrosis of the jaw (ONJ). In this study, we aimed to elucidate the mechanism of ONJ.
ONJ typically appears as an area of exposed alveolar bone that can occur in the mandible or the maxilla. We hypothesis that pathogen in oral cavity might be involved in the etiology of ONJ, and focused to toll like receptors (TLRs), which recognize microviral antigens to provoke innate immunity and establish adaptive immunity.
TLR3 stably expressed in osteoblastic MC3T3-E1 cells. Poly (I):poly (C) induced interferon-β (IFN-β) mRNA, and which enhanced TLR3 expression in autocrin manner via IFN-α/β receptor, IFNAR, following by STAT1 phosphorylation.
LPS treatment decrease in cell viability in pamidronate-pretreated macrophage-like RAW 264 cells. Moreover, high concentration of pamidronate and zoledronic acid suppressed inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α. High concentration Bps might suppress innate immunity system in the osteoblasts.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (17 results)

All 2008 2007

All Journal Article (5 results) (of which Peer Reviewed: 3 results) Presentation (12 results)

  • [Journal Article] Novel effect of estrogen on RANK and c-fms expression in RAW 264.7 cells.2008

    • Author(s)
      Galal N, El-Beialy WR, Deyama Y, Yoshimura Y, Suzuki K, Totsuka Y.
    • Journal Title

      Int J Mol Med 21(3)

      Pages: 291-296

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Novel effect of estrogen on RANK and -c-fms expression in RAW 264.7 cells.2007

    • Author(s)
      Nadia Galal
    • Journal Title

      Int J Mol Med. 21

      Pages: 97-101

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Toll-like receptor 3 ligand-induced antiviral response in mouse osteoblastic cells.2007

    • Author(s)
      中村 公也
    • Journal Title

      Int J Mol Med. 19

      Pages: 771-775

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Toll-like receptor 3 ligand-induced antiviral response in mouse osteoblastic cells.2007

    • Author(s)
      Nakamura K, Deyama Y, Yoshimura Y, Suzuki K, Morita M.
    • Journal Title

      Int J Mol Med 19(5)

      Pages: 771-775

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Novel effect of estrogen on RANK and c-fms expression in RAW 264.7 cells.2007

    • Author(s)
      Nadia Galal
    • Journal Title

      Int J Mol Med. 21

      Pages: 97-101

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 骨芽細胞における自然免疫系シグナル2008

    • Author(s)
      出山 義昭
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2008-03-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Innate immunity signal in osteoblast2008

    • Author(s)
      Deyama Y, Nakamura K, Yoshimura Y, Nakamura K, Tei K, Totsuka Y, Suzuki K
    • Organizer
      The 81th Annual Meeting of The Japanese Pharmacological Society
    • Place of Presentation
      Pacifico Yokohama (Yokohama)
    • Year and Date
      2008-03-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] MC3T3-E1細胞におけるTLR3リガンドによるRIG-Iの発現誘導2007

    • Author(s)
      出山 義昭
    • Organizer
      第30回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2007-12-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 「研究成果報告書概要(欧文)」より2007

    • Author(s)
      Nakamura K, Deyama Y, Yoshimura Y, Suzuki K, Morita M
    • Organizer
      The 30^<th> Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      Pacifico Yokohama (Yokohama)
    • Year and Date
      2007-12-11
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Toll様受容体を介したシグナルの骨芽細胞における機能2007

    • Author(s)
      出山 義昭
    • Organizer
      第58回日本薬理学会北部会
    • Place of Presentation
      北海道大学(札幌)
    • Year and Date
      2007-09-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Function of TLR signaling in osteoblast2007

    • Author(s)
      Deyama Y, Nakamura K, Yoshimura Y, Morita M, Suzuki K
    • Organizer
      The 58^<th> North Blanch Meeting of The Japanese Pharmacological Society
    • Place of Presentation
      Hokkaido University (Sapporo)
    • Year and Date
      2007-09-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 骨芽細胞様細胞に対するTLRリガンドの効果2007

    • Author(s)
      出山 義昭
    • Organizer
      動物サイトカイン研究会 第5回学術集会
    • Place of Presentation
      酪農学園大学(江別)
    • Year and Date
      2007-09-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Effects of TLR ligands on osteoblasts2007

    • Author(s)
      Nakamura K, Deyama Y, Yoshimura Y, Suzuki K, Morita M
    • Organizer
      5^<th> Annual Meeting of The Japanese Society for Animal Cytokine Research
    • Place of Presentation
      Rakuno Gakuen University (Ebetsu)
    • Year and Date
      2007-09-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 骨芽細胞様MC3T3-E1細胞におけるRIG-Iの発現2007

    • Author(s)
      出山 義昭
    • Organizer
      第49回歯科基礎医学会学術大会ならびに総会
    • Place of Presentation
      北海道大学(札幌)
    • Year and Date
      2007-08-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Estrogen and joint disorders2007

    • Author(s)
      出山 義昭
    • Organizer
      第49回歯科基礎医学会学術大会ならびに総会
    • Place of Presentation
      北海道大学(札幌)
    • Year and Date
      2007-08-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Expression of RIG-I in osteoblastic MC3T3-E1 cells2007

    • Author(s)
      Nakamura K, Deyama Y, Yoshimura Y, Suzuki K, Morita M
    • Organizer
      49th Annual Meeting of Japanese Association for Oral Biology
    • Place of Presentation
      Hokkaido University (Sapporo)
    • Year and Date
      2007-08-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Estrogen and joint disorders2007

    • Author(s)
      Galal N, E1-Beialy WR, Deyama Y, Yoshimura Y, Suzuki K, Totsuka Y
    • Organizer
      49th Annual Meeting of Japanese Association for Oral Biology
    • Place of Presentation
      Hokkaido University (Sapporo)
    • Year and Date
      2007-08-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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