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Elucidation of molecular mechanism of alveolar bone remodeling induced by orthodontic force.

Research Project

Project/Area Number 17592155
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthodontic/Pediatric dentistry
Research InstitutionMatsumoto Dental University

Principal Investigator

KURIHARA Saburo  Matsumoto Dental University, Department of dentistry, Professor, 歯学部, 教授 (70126225)

Co-Investigator(Kenkyū-buntansha) OKAFUJI Norimasa  Matsumoto Dental University, Department of dentistry, Associate Professor, 歯学部, 助教授 (50194379)
UEMATSU Setsuo  Matsumoto Dental University, Department of dentistry, Lecturer, 歯学部, 講師 (80271378)
TAKAHASHI Naoyuki  Matsumoto Dental University, Institute of Oral Science, Professor, 大学院歯学独立研究科, 教授 (90119222)
UDAGAWA Nobuyuki  Matsumoto Dental University, Department of dentistry, Professor, 歯学部, 教授 (70245801)
NAKAMURA Hiroaki  Matsumoto Dental University, Department of dentistry, Professor, 歯学部, 教授 (50227930)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsOsteoclast / Albeolar bone resorption / Human osteoclasts / PGE_2 / EP2 / EP4 / CD14-positive cells / Osteoclast progenitors / BMP / 骨芽細胞 / RANKL / op / opマウス / リゼドロネート / OPG / カルシトニン / ビスフォスホネート
Research Abstract

We have performed three experiments to elucidate the molecular mechanism by which alveolar bone remodeling induced by orthodontic force. The role of prostaglandin E2 (PGE_2) in osteoclastic bone resorption was carefully examined in this program.
Exp. 1 : PGE_2 synergistically enhances RANKL-induced osteoclastic differentiation of the precursor cells. We investigated the mechanisms of the stimulatory effect of PGE_2 on osteoclast differentiation. The stimulatory effect of PGE_2 on the RANKL-induced osteoclast differentiation of the precursor cells was mediated through EP2 and EP4. TAK1 acted as an adapter molecule linking PKA-induced signals and RANKL-and TNFα-induced such signals in osteoclast precursors. Furthermore, TAK1 is involved in the synergistic effect of cAMP/PKA signals on TNF receptor-and Toll-like receptor 4 (TLR4)-induced signaling pathways. The cAMP/PKA signal may enhance bone resorption induced by RANKL and TNFα through TAK1 in osteoclast precursors.
Exp. 2 : PGE_2 itself … More has been shown to directly inhibit bone-resorbing activity of osteoclasts. We explored the mechanism of PGE_2 action in the osteoclastic differentiation of precursor cells. The stimulatory effect of PGE_2 on the RANKL-induced osteoclast differentiation of the precursor cells was mediated through EP2 and EP4. TAK1 acted as an adapter molecule linking PKA-induced signals and RANKL-and TNFα-induced such signals in osteoclast precursors. Furthermore, TAK1 is involved in the synergistic effect of cAMP/PKA signals on TNF receptor-and Toll like receptor 4 (TLR4)-induced signaling pathways. The cAMP/PKA signal may enhance bone resorption induced by RANKL and TNFα through TAK1 in osteoclast precursors.
Exp. 3 : We explored the role of PGE_2 in human osteoclast differentiation in more detail. Unlike mouse macrophage cultures, PGE_2 strongly inhibited RANKL-induced osteoclast formation in human CD14^+ cell cultures. Human osteoclast progenitors produced a soluble unidentified factor(s) in response to PGE_2, which strongly inhibited RANKL-induced osteoclast formation in not only human CD14^+ cell cultures but also mouse macrophage cultures. These results suggest that COX-2 inhibitors may not be suitable therapeutic agents to suppress osteoclastic bone resorption in inflammatory bone diseases. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (18 results)

All 2007 2006 2005 2004

All Journal Article (17 results) Book (1 results)

  • [Journal Article] Effect of age on alveolar bone turnover adjacent to maxillary molar roots in male rats : A histomorphometric study.2007

    • Author(s)
      Misawa Y et al.
    • Journal Title

      Arch Oral Biol 52・(1)

      Pages: 44-50

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Tissue reaction to poly (lactic-co-glycolic acid) copolymer membrane in rhBMP used rabbit experimental mandibular reconstruction.2006

    • Author(s)
      Okafuji N et al.
    • Journal Title

      Eur J Med Res 11・(9)

      Pages: 394-396

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Three-dimensional observation of reconstruction course of rabbit experimental mandibular defect with rhBMP-2 and atelocollagen gel.2006

    • Author(s)
      Okafuji N et al.
    • Journal Title

      Eur J Med Res 11・(8)

      Pages: 351-354

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Cephalometric study of elderly with nearly intact dental arches.2006

    • Author(s)
      Shimizu T et al.
    • Journal Title

      Gerodontology 23・(1)

      Pages: 60-63

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Tissue reaction to poly (lactic-co-glycolic acid) copolymer membrane in rhBMP used rabbit experimental mandibular reconstruction.2006

    • Author(s)
      Okafuji N et al.
    • Journal Title

      Eur J Med Res 11 (9)

      Pages: 394-396

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Three-dimensional observation of reconstruction course of rabbit experimental mandibular defect with rhBMP-2 and atelocollagen gel.2006

    • Author(s)
      Okafuji N et al.
    • Journal Title

      Eur J Med Res 11(8)

      Pages: 351-354

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cephalometric study of elderly with nearly intact dental arches.2006

    • Author(s)
      Shimizu T et al.
    • Journal Title

      Gerodontology 23(1)

      Pages: 60-63

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tissue reaction to poly (lactic-co-glycolic acid) copolymer membrane in rhBMP used rabbit experimental mandibular reconstruction2006

    • Author(s)
      Okafuji N et al.
    • Journal Title

      Eur J Med Res 11・(9)

      Pages: 394-396

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression of Notchl and Mathl in mandibular condyle cartilage in neonatal mice.2005

    • Author(s)
      Shimizu T et al.
    • Journal Title

      Angle Orthod 75・(6)

      Pages: 993-995

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of Notch1 and Math1 in mandibular condyle cartilage in neonatal mice.2005

    • Author(s)
      Shimizu T et al.
    • Journal Title

      Angle Orthod 75(6)

      Pages: 993-995

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of Notch1 and Math1 in Mandibular Condyle Cartilage in Neonatal Mice.2005

    • Author(s)
      Shimizu T
    • Journal Title

      Angl Orthodont 75・6

      Pages: 993-995

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prostaglandin E_2 enhances osteoclastic differentiation of precursor cells through protein kinase A-dependent phosphorylation of TAK1.2005

    • Author(s)
      Kobayashi Y
    • Journal Title

      J Biol Chem 280・12

      Pages: 11395-11403

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prostaglandin E_2 receptors EP2 and EP4 are down-regulated during differentiation of mouse osteoclasts from their precursors.2005

    • Author(s)
      Kobayashi Y
    • Journal Title

      J Biol Chem 280・25

      Pages: 24035-24042

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Muramyl dipeptide enhances osteoclast formation induced by lipopolysaccharide, IL-1α and TNF-1α through nucleotide-binding oligomerization domain 2-mediated signaling in osteoblasts.2005

    • Author(s)
      Yang S
    • Journal Title

      J Immunol 175・3

      Pages: 1956-1964

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prostaglandin E_2 strongly inhibits human osteoclast formation.2005

    • Author(s)
      Take I
    • Journal Title

      Endocrinology 146・12

      Pages: 5204-5214

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nurse-like cells from patients with rheumatoid arthritis support survival of osteoclast precursors via macrophage-colony stimulating factor production.2005

    • Author(s)
      Tsuboi H
    • Journal Title

      Arthritis Rheum 52・12

      Pages: 3819-3828

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of age on alveolar bone turnover adjacent to maxillary molar roots in male rats : A histomorphometric study.2004

    • Author(s)
      Misawa Y et al.
    • Journal Title

      Arch Oral Biol 52(1)

      Pages: 44-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Hard Tissue 硬組織研究ハンドブック2005

    • Author(s)
      松本歯科大学大学院 硬組織研究グループ
    • Total Pages
      261
    • Publisher
      MDU出版会
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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