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Isolation and identification of bone morphogentic protein and its potentiator from bovine serum

Research Project

Project/Area Number 16390533
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionSaitama Medical School

Principal Investigator

KATAGIRI Takenobu  Saitama Medical School, School of Medicine, Associate Professor, 医学部, 助教授 (80245802)

Co-Investigator(Kenkyū-buntansha) SUDA Tatsuo  Saitama Medical School, School of Medicine, Professor, 医学部, 教授 (90014034)
KAMIJO Ryutaro  Showa University, School of Dentistry, Professor, 歯学部, 教授 (70233939)
FUKUDA Toru  Saitama Medical School, School of Medicine, Research Associate, 医学部, 助手 (20301492)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2005: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2004: ¥8,600,000 (Direct Cost: ¥8,600,000)
Keywordsserum / protein / osteoblast differentiation / bone formation / platelet / 生体成分 / 血清 / 骨誘導因子 / 骨芽細胞 / 分化
Research Abstract

We purified a protein factor, which potentiates osteoblast differentiation, from fetal bovine serum. Although this factor itself did not show such stimulatory activity, it stimulated the osteoblast differentiation in the presence of small amount of bone morphogenetic proteins (BMPs), suggesting that this factor is a BMP potentiator. This factor is derived from platelets. Deficient mice in this factor expression showed delayed bone fracture hearing. In contrast, the fracture hearing was accelerated in transgenic mice of this factor. Moreover, we found a BMP-like factor in fetal bovine serum and isolated this activity using a series of column chromatography. The biological activity of this serum BMP was blocked by dominant negative form of BMP receptor and Noggin, a BMP antagonist. LC-MS/MS analysis indicated that the highly purified fraction contained a conserved sequence of a mature BMP. These results indicate that serum factors play a important role in bone formation. Moreover, we found that sulfated polysaccharides such as heparin and heparan sulfate also potentiated the biological activities of BMPs. When BMP was implanted together with heparin in mice, the ectopic bone-inducing activity of BMP in vivo was also potentiated by heparin. Taken together, it was suggested that BMPs and their potentiators in serum positively regulate bone formation in vertebrates.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (34 results)

All 2006 2005 2004 Other

All Journal Article (32 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Surface chemistry and biological responses to synthetic octacalcium phosphate2006

    • Author(s)
      Suzuki O., et al.
    • Journal Title

      J. Biomed. Mater. Res. B Appl. Biomater. 77B

      Pages: 201-212

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bone formation enhanced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite2006

    • Author(s)
      Suzuki O., et al.
    • Journal Title

      Biomaterials 27

      Pages: 2671-2681

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] BMPと骨代謝疾患のゲノム学2006

    • Author(s)
      片桐岳信, 福田 亨
    • Journal Title

      ゲノム医学 6

      Pages: 39-43

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MBP応答遺伝子の転写制御2006

    • Author(s)
      片桐岳信, 他
    • Journal Title

      クリニカルカルシウム (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Surface chemistry and biological responses to synthetic octacalcium phosphate.2006

    • Author(s)
      Suzuki O., et al.
    • Journal Title

      J.Biomed.Mater.Res.B Appl.Biomater. 77B

      Pages: 201-212

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bone formation enhanced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite.2006

    • Author(s)
      Suzuki O., et al.
    • Journal Title

      Biomaterials 27

      Pages: 2671-2681

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Establishment of a novel method for enriching osteoblast progenitors from adipose tissues using a difference in cell adhesive properties.2006

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

      Biochem.Biophys.Res.Commun. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] BMPs and their genetic diseases.2006

    • Author(s)
      Katagiri T., Fukuda T.
    • Journal Title

      Genomic Medicine 6

      Pages: 39-43

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional regulations of BMP-responsive genes2006

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

      Clinical Calcium (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Surface chemistry and biological responses to synthetic octacalcium phosphate.2006

    • Author(s)
      Suzuki, O., Kamakura, S., Katagiri. T.
    • Journal Title

      J Biomed Mater Res B Appl Biomater

      Volume: 77B Pages: 201-212

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bone formation enhanced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite.2006

    • Author(s)
      Suzuki, S., Kamakura, S., Katagiri, T., Nakamura, M., Zhao B., Honda, Y., Kamijo.
    • Journal Title

      Biomaterials

      Volume: 27 Pages: 2671-2681

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enamel Matrix Derivative Gel Stimulates Signal Transduction of BMP and TGF-β2005

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

      J. Dent. Res. 84

      Pages: 510-514

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of endogenous bone morphogenetic protein (BMP)2 and BMP6 in bone formation2005

    • Author(s)
      Kugimiya F., et al.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 35704-35712

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cross-talk between Wnt and bone morphogenetic protein (BMP)-2 signaling in differentiation pathway of C2C12 myoblasts2005

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

      J. Biol. Chem. 280

      Pages: 37660-37668

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 骨形成のメカニズムと骨形成促進薬2005

    • Author(s)
      片桐岳信, 福田 亨
    • Journal Title

      クリニカルカルシウム 15

      Pages: 1115-1120

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] BMPアンタゴニストの発見と機能2005

    • Author(s)
      片桐岳信, 福田 亨
    • Journal Title

      日本臨床 63

      Pages: 404-408

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enamel Matrix Derivative Gel Stimulates Signal Transduction of BMP and TGF-β.2005

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

      J.Dent.Res. 84

      Pages: 510-514

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of endogenous bone morphogenetic protein (BMP)2 and BMP6 in bone formation.2005

    • Author(s)
      Kugimiya F., et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 35704-35712

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cross-talk between Wnt and bone morphogenetic protein (BMP)-2 signaling in differentiation pathway of C2C12 myoblasts.2005

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

      J.Biol.Chem. 280

      Pages: 37660-37668

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular mechanisms of bone formation and bone fomation-stimuratory drugs.2005

    • Author(s)
      Katagiri T.
    • Journal Title

      Clinical Calcium 15

      Pages: 1115-1120

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] BMP antagonists.2005

    • Author(s)
      Katagiri T., Fukuda T.
    • Journal Title

      Nippon Rinsho 63

      Pages: 404-408

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enamel Matrix Derivative Gel Stimulates Signal Transduction of BMP and TGF-β.2005

    • Author(s)
      Suzuki, S., Nagano, T., Yamakoshi, Y., Gomi, K., Arai, T., Fukae, M., Katagiri, T., Oida, S.
    • Journal Title

      J Dent Res

      Volume: 84 Pages: 510-514

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Involvement of endogenous bone morphogenetic protein (BMP)2 and BMP6 in bone formation.2005

    • Author(s)
      Kugimiya, F., Kawaguchi, H., Kamekura, S., Chikuda, H., Ohba, S., Yano, F., Ogata, N., Katagiri, T., Harada, Y., Azuma, Y., Nakamura, K., Chung, U.-I.
    • Journal Title

      J Biol Chem

      Volume: 280 Pages: 35704-35712

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cross-talk between Wnt and bone morphogenetic protein (BMP)-2 signaling in differentiation pathway of C2C12 myoblasts.2005

    • Author(s)
      Nakashima, A., Katagiri. T., Tamura, M.
    • Journal Title

      J Biol Chem

      Volume: 280 Pages: 37660-37668

    • Related Report
      2005 Annual Research Report
  • [Journal Article] BMPアンタゴニストの発現と機能.2005

    • Author(s)
      片桐岳信、福田亨
    • Journal Title

      日本臨床

      Volume: 63 Pages: 404-408

    • Related Report
      2005 Annual Research Report
  • [Journal Article] BMPアンタゴニストの発現と機能2005

    • Author(s)
      片桐岳信, 福田 亨
    • Journal Title

      日本臨床 (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enhnacement of biological activity of BMP by heparin2004

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

      Biological Mechanisms of Tooth Movement and Craniofacial Adaptation

      Pages: 201-207

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] BMP2004

    • Author(s)
      片桐岳信
    • Journal Title

      骨粗鬆症治療 3

      Pages: 337-341

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enhnacement of biological activity of BMP by heparin.2004

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

      Biological Mechanisms of Tooth Movement and Craniofacial Adaptation

      Pages: 201-207

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heparin enhances the biological activities of bone morphogenetic proteins2004

    • Author(s)
      Takada T, Katagiri T, Morimura N, et al.
    • Journal Title

      Biol.Mech.Tooth Mov.Craniofac.Adap.

      Pages: 201-207

    • Related Report
      2004 Annual Research Report
  • [Journal Article] BMP2004

    • Author(s)
      片桐岳信
    • Journal Title

      骨粗鬆症治療 3(4)

      Pages: 338-344

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Establishment of a novel method for enriching osteoblast progenitors from adipose tissues using a difference in cell adhesive properties

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

      Biochem. Biophys. Res. Commun. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 動脈硬化の治療剤2005

    • Inventor(s)
      須田立雄, 片桐岳信, 東尾侃二, 後藤雅昭, 小平邦彦
    • Industrial Property Rights Holder
      埼玉医学大学, 中外製薬
    • Industrial Property Number
      2005-198977
    • Filing Date
      2005-07-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 動脈硬化の治療剤2005

    • Inventor(s)
      須田立雄、片桐岳信、東尾侃二、後藤雅昭、小平邦彦
    • Industrial Property Rights Holder
      埼玉医科大学、中外製薬
    • Industrial Property Number
      2005-198977
    • Filing Date
      2005-07-07
    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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