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Analysis of molecular mechanisms in bone formation and regeneration

Research Project

Project/Area Number 14207075
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionMatsumoto Dental University

Principal Investigator

OZAWA Hidehiro  Matsumoto Dental University, Graduate school of Oral Medicine, Professor, 大学院・歯学独立研究科, 教授 (60018413)

Co-Investigator(Kenkyū-buntansha) KAWAKAMI Toshiyuki  Matsumoto Dental University, Graduate school of Oral Medicine, Professor, 大学院・歯学独立研究科, 教授 (80104892)
TAKAHASHI Naoyuki  Matsumoto Dental University, Graduate school of Oral Medicine, Professor, 大学院・歯学独立研究科, 教授 (90119222)
UDAGAWA Nobuyuki  Matsumoto Dental University, Graduate school of Oral Medicine, Professor, 歯学部, 教授 (70245801)
KAWAGUCHI Hiroshi  The University of Tokyo, Department of Orthopedics, Assistant professor, 医学部附属病院, 助教授 (40282660)
HOSOYA Akihiro  Matsumoto Dental University, Department of Oral Histology, Associate professor, 歯学部, 助手 (70350824)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥50,180,000 (Direct Cost: ¥38,600,000、Indirect Cost: ¥11,580,000)
Fiscal Year 2004: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2003: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2002: ¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000)
KeywordsCalcification / Bone formation / Bone resorption / Coupling factor / MyD88 / Dental pulp / Laser / EP4 agonist / BMP / OPG / EP4 / 急速凍結法
Research Abstract

I. Molecular mechanisms of calcification in bone matrix formation : To identify the factor induce formation of the nuclear, we make monoclonal anti-body using matrix vesicle isolated from MLO-A5 cell in culture and clarified that the antigen localizes among the fibrae in extracellular matrix. Moreover, to estimate the effects of Mg in bone calcification, we determined the bone qualities, especially mineralization in Mg deficient rat. Loss of Mg was increased the value of Ca and had irregular crystal of hydroxyapatite in the rat. These findings indicate that the loss of Mg inhibits the crystallization of hydroxyapatite in matrix vesicle.
II. Coupling mechanisms of bone metabolism : Bone formation and bone resorption were promoted in osteoprotegerin (OPG)-deficient mice. Bisphosphonate, a potential inhibitor of bone resorption, reduced both bone formation and bone resorption. Bone formation induced by bone morphogenetic protein in OPG-deficient mice did not exhibit any difference from tha … More t in wild mice. These results suggest that coupling factors activated or released by osteoclasts may be involved in the subsequent bone formation. We investigated the mechanism of osteoclastogenesis induced by lipopolysaccharide and interleukin (IL)-1. These factors induced the expression of RANKL in osteoblastic cells through MyD 88 and Ca/PKC-MEK/ERK pathways.
III. Bone regeneration and reconstruction model : The subcutaneously transplanted rat dental pulp formed mineralized hard tissue possessing bone- or cementum-like characteristics, suggesting that dental pulp possesses the ability to hard tissue formation by itself. Bone formation induced laser light irradiation was shown to be caused by the odontoblast activation and the inhibition of osteoclastic bone resorption. In the study of prostaglandin E EP4 receptor agonist, the gene expression existed in odontoblast, and the bone formation activity was resulted from the decrease of adipocyte and the increase of osteoblast in bone marrow. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (50 results)

All 2005 2004 2003 2002 Other

All Journal Article (36 results) Book (1 results) Publications (13 results)

  • [Journal Article] Effects of fixation and decalcification on the immunohistochemical localization of bone matrix proteins in fresh-frozen bone sections.2005

    • Author(s)
      Hosoya, A., et al.
    • Journal Title

      Histochem Cell Biol. 121(In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes.2005

    • Author(s)
      Chikuda, H., et al.
    • Journal Title

      Genes Dev. 18

      Pages: 2418-2429

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Calcification, as a key step in bone formation and regeneration.2005

    • Author(s)
      Hoshi, K., et al.
    • Journal Title

      Anat Sci Int. 79

      Pages: 115-115

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of fixation and decalcification on the immunohistochemical localization of bone matrix proteins in fresh-frozen bone sections.2005

    • Author(s)
      Hosoya A., et al.
    • Journal Title

      Histochem Cell Biol (in press)

      Pages: 121-121

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes.2005

    • Author(s)
      Chikuda H., et al.
    • Journal Title

      Genes Dev 18

      Pages: 2418-2429

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostaglandin E2 enhances osteoclastic differentiation of precursor cells through protein kinase A-dependent phosphorylation of TAK 12005

    • Author(s)
      Kobayashi, Y., et al.
    • Journal Title

      J Biol Chem. 280(In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of fixation and decalcification on the immunohistochemical localization of bone matrix proteins in fresh-frozen bone sections2005

    • Author(s)
      Hosoya, A., et al.
    • Journal Title

      Histochem Cell Biol. 123(In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes2005

    • Author(s)
      Kawaguchi, H., et al.
    • Journal Title

      Genes Dev. 18・19

      Pages: 2418-2429

    • Related Report
      2004 Annual Research Report
  • [Journal Article] MyD88 but not TRIF is essential for osteoclastogenesis induced by lipopolysaccharide, diacyl lipopeptide, and IL-1alpha.2004

    • Author(s)
      Sato, N., et al.
    • Journal Title

      J Exp Med. 200

      Pages: 601-611

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histochemical evaluation for the biological effect of menatetrenone on metaphyseal trabeculae of ovariectomized rats.2004

    • Author(s)
      Asawa, Y., et al.
    • Journal Title

      Bone. 35

      Pages: 870-880

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of Notch in a case of osteosarcoma of the maxilla.2004

    • Author(s)
      Kawakami, T., et al.
    • Journal Title

      Eur J Med Res. 9

      Pages: 533-535

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6.2004

    • Author(s)
      Ogasawara, T., et al.
    • Journal Title

      Mol Cell Biol. 24

      Pages: 6560-6568

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Periodontal regeneration of transplanted rat molars after cryopreservation.2004

    • Author(s)
      Kawasaki, N., et al.
    • Journal Title

      Arch Oral Biol. 49

      Pages: 59-69

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostaglandin E EP4 receptor agonist induces the bone formation by an alteration of the osteoblast and osteoclast dynamic state.2004

    • Author(s)
      Tanaka, M., et al.
    • Journal Title

      J Toxicol Pathol. 17

      Pages: 253-260

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MyD88 but not TRIF is essential for osteoclastogenesis induced by lipopolysaccharide, diacyl lipopeptide, and IL-1alpha.2004

    • Author(s)
      Sato N., et al.
    • Journal Title

      J Exp Med 200

      Pages: 601-611

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Calcification, as a key step in bone formation and regeneration.2004

    • Author(s)
      Hoshi K., et al.
    • Journal Title

      Anat Sci Int 79

      Pages: 115-115

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histochemical evaluation for the biological effect of menatetrenone on metaphyseal trabeculae of ovariectomized rats.2004

    • Author(s)
      Asawa Y., et al.
    • Journal Title

      Bone 35

      Pages: 870-880

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of Notch in a case of osteosarcoma of the maxilla.2004

    • Author(s)
      Kawakami T., et al.
    • Journal Title

      Eur J Med Res 9

      Pages: 533-535

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6.2004

    • Author(s)
      Ogasawara T., et al.
    • Journal Title

      Mol Cell Biol 24

      Pages: 6560-6568

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Periodontal regeneration of transplanted rat molars after cryopreservation.2004

    • Author(s)
      Kawasaki N., et al.
    • Journal Title

      Arch Oral Biol 49

      Pages: 59-69

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostaglandin E EP4 receptor agonist induces the bone formation by an alteration of the osteoblast and osteoclast dynamic state.2004

    • Author(s)
      Tanaka M., et al.
    • Journal Title

      J Toxicol Pathol 17

      Pages: 253-260

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histochemical evaluation for the biological effect of menatetrenone on metaphyseal trabeculae of ovariectomized rats.2004

    • Author(s)
      Asawa, Y., et al.
    • Journal Title

      Bone. 35・4

      Pages: 870-880

    • Related Report
      2004 Annual Research Report
  • [Journal Article] MyD88 but not TRIF is essential for osteoclastogenesis induced by lipopolysaccharide, diacyl lipopeptide, and IL-1alpha.2004

    • Author(s)
      Sato, N., et al.
    • Journal Title

      J Exp Med. 200・5

      Pages: 601-611

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of Notch in a case of osteosarcoma of the maxilla.2004

    • Author(s)
      Kawakami, T., et al.
    • Journal Title

      Eur J Med Res. 9・11

      Pages: 533-535

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption.2003

    • Author(s)
      Nakamura, M., et al.
    • Journal Title

      Endocrinology. 144

      Pages: 5441-5449

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene expression of type I collagen in neoplastic chondrocytes.2003

    • Author(s)
      Kimura, A., et al.
    • Journal Title

      Eur J Med Res. 8

      Pages: 165-167

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An immunohistochemical study on hard tissue formation in a subcutaneously transplanted rat molar.2003

    • Author(s)
      Hosoya, A., et al.
    • Journal Title

      Histochem Cell Biol. 119

      Pages: 27-35

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption.2003

    • Author(s)
      Nakamura M., et al.
    • Journal Title

      Endocrinology 144

      Pages: 5441-5449

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene expression of type I collagen in neoplastic chondrocytes.2003

    • Author(s)
      Kimura A., et al.
    • Journal Title

      Eur J Med Res 8

      Pages: 165-167

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An immunohistochemical study on hard tissue formation in a subcutaneously transplanted rat molar.2003

    • Author(s)
      Hosoya A., et al.
    • Journal Title

      Histochem Cell Biol 119

      Pages: 27-35

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of ovariectomy on trabecular structures of rat alveolar bone.2002

    • Author(s)
      Tanaka, M., et al.
    • Journal Title

      J Periodontal Res. 37

      Pages: 161-165

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of estrogen deficiency on osteoclastgenesis in rat peiodontium.2002

    • Author(s)
      Kawamoto, S., et al.
    • Journal Title

      Arch Oral Biol. 47

      Pages: 67-73

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Immunohistochemical study on pulpal response in rat molars after cavity preparation by Er : YAG laser.2002

    • Author(s)
      Tanabe, K., et al.
    • Journal Title

      Eur J Oral Sci. 110

      Pages: 237-245

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of ovariectomy on trabecular structures of rat alveolar bone.2002

    • Author(s)
      Tanaka M., et al.
    • Journal Title

      J Periodontal Res 37

      Pages: 161-165

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of estrogen deficiency on osteoclastogenesis in rat peiodontium.2002

    • Author(s)
      Kawamoto S., et al.
    • Journal Title

      Arch Oral Biol 47

      Pages: 67-73

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Immunohistochemical study on pulpal response in rat molars after cavity preparation by Er : YAG laser.2002

    • Author(s)
      Tanabe K., et al.
    • Journal Title

      Eur J Oral Sci 110

      Pages: 237-245

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 硬組織研究ハンドブック2005

    • Author(s)
      小澤英浩, 他
    • Total Pages
      264
    • Publisher
      松本歯科大学出版会
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Amizuka, N., et al.: "Signalling by fibroblast growth factor receptor 3 and parathyroid hormone-related peptide coordinate cartilage and bone development"Bone. 34・1. 13-25 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mochizuki, R., et al.: "Targeted disruption of the neurochondrin/norbin gene results in embryonic lethality"Biochem.Biophys.Res.Commun.. 310・4. 1219-1226 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Gong, L., et al.: "Bisphosphonate incadronate inhibits maturation of ectopic bone induced by recombinant human bone morphogenetic protein 2"J Bone Miner Metab.. 21・4. 5-11 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kimura, A., et al.: "Gene expression of type I collagen in neoplastic chondrocytes"Eur J Med Res.. 8・4. 165-167 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahashi, N., et al.: "Strontium ranelate inhibits osteoclastic bone resorption"J Bone Miner Res.. 18・6. 1082-1087 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamura, M., et al.: "Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption"Endocrinology. 144・12. 5441-5449 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ozawa H et al.: "Effect of streptozotocin-induced diabetes mellitus on alveolar bone deposition in the rat"Archives of Oral Biology. 47. 843-849 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ozawa H et al.: "1α,25-dihydroxyvitamin D3 promotes vascularization of the chondro-osseous junction by stimulating expression of vascular endothelial growth factor and matrix metalloproteinase 9"J.Bone Miner Res.. 17(9). 1604-1612 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ozawa H et al.: "An immunohistochemical study on hard tissue formation in a subcutaneously transplanted rat molar"Histochemistry and Cell Biology. 119. 27-35 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Udagawa N et al.: "The molecular mechanism of bone destruction in rheumatoid arthritis"Arthritis Research. 4. 281-289 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Amizuka N et al.: "The biological action of parathyroid hormone (PTH) -related peptide (PTHrP) mediated either by the PTH/PTHrP receptor or the nucleolar translocation in chondrocytes"Anat.Sci.Int.. 77(4). 225-236 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawakami T et al.: "Localization of Matrix Proteins of Hard Tissue in Osteochondromas"Eur J Med Res.. 7. 335-339 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi N et al.: "Principles of Bone Biology, Second Edition, Volume 1"Academic press. 882 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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