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Analysis concerning the mechanisms of differentiation in the bone marrow stromal cells after bone implantatio

Research Project

Project/Area Number 11671429
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionShinshu University

Principal Investigator

TAKAOKA Kunio (2000-2001)  Shinshu University, School of Medicine, Professor, 医学部, 教授 (30112048)

吉村 康夫 (1999)  信州大学, 医学部・附属病院, 助手 (10303439)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Tominaga  Shinshu University, School of Medicine, 医学部・附属病院, 助手 (40283270)
SAITO Naoto  Shinshu University, School of Medicine, 医学部, 講師 (80283258)
高岡 邦夫  信州大学, 医学部, 教授 (30112048)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsAutograft / Bone formation / Bone marrow cells / BMP / Noggin / TNF-α / Pentoxifylline / 骨形成因子(BMP-4)
Research Abstract

First, we examined the temporal and spatial expression of bone morphogenetic protein-4 ( BMP-4 ) in bone tissue and compared with that of noggin ( inhibitory factor for BMP ) in mice with fractures by means of northern blotting and in situ hybridization. BMP-4 and noggin were colocaI ized in the process of fracture repair, and expression levels of those mRNA were enhanced in the early phase.
We investigated bone formation for the bone marrow cells ( obtained from femur in rats ) in the diffusion chamber embedded to paravertebraI muscle in rats. Bone marrow cells in the diffusion chamber have attached on the inner surface on 1 or 2 weeks after implantation. And those differentiated and proliferated into chondrocytes and osteoblasts until 4 weeks after implantation. This process was similar to that of fracture repair. The expression of BMP-4 mRNA was detected in the osteoprogenitor cells, chondrocytes and osteoblasts in the diffusion chamber. These findings suggest that bone marrow cells have bone induction activity with autocrine mechanism for BMPs.
We examined about the effect for increasing bone mass by using pentoxifylline ( This drug inhibits the action of tumor necrosis factor-alpha ). The femurs in mice had osteoporotic change after administration of lipopolysaccharide ( LPS ) , but this phenomenonwas inhibited with pentoxifylline. And the effect for increasing bone mass was detected in normal mice with using pentoxifylline only. Furthermore, we confirmed that the ectopic bone induction activity with recombinant BMP-2 was enhanced by using pentoxifylline.

Report

(3 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Yoshimura Y., Takaoka K: "Colocalization of Noggin and Bone Morphogenetic Protein-4 during Fracture Healing"Journal of Bone and Mineral Research. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Horiuchi H., Takaoka K: "Enhancement of Bone Morphogenetic Protein-2 Induced New Bone Formation in mice by a Phosphodiesterase Inhibitor, Pentoxifylline"Bone. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saitou N., Takaoka K.: "A biodegradable polymer as a cytokine delivery system for inducing bone formation"Nature Biotechnology. 19(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kinoshita T., Takaoka K.: "Phosphodiesterase inhibitors, pentoxyfylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice"Bone. 27. 811-817 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawasaki S., Takaoka K.: "The E-box motif, recognized by tissue-specific nuclear factor(s), is important for BMP-4 gene expression"Biochemical and Biophysical Research Communication. 263. 560-565 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsutsumimoto T, Takaoka K.: "IL-1 and TNF-α suppress N-cadherin expression in MC3T3-E1 cells"り. 14. 1751-1760 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsutsumimoto,T., Takaoka,K.: "IL-1 and TNF-α suppress N-cadherin expression in MC3T3-E1 cells"J Bone Miner Res. 14. 1751-1760 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawasaki,S., Takaoka,K.: "The E-box motif, recognized by tissue-specific nuclear factor(s), is.mportant for BMP-4 gene expression"Biochem Biophys Res Comm. 263. 560-565 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kinoshita,T., Takaoka,K.: "Phosphodiesterase inhibitors, pentoxyfylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice"Bone. 27. 811-817 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saitou,N., Takaoka,K.: "A biodegradable polymer as a cytokine delivery system for inducing bone formation"Nature Biotechnology. 19 ( in press ). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Horiuchi,H., Takaoka,K.: "Enhancement of Bone Morphogenetic Protein-2 Induced New Bone Formation in mice by a Phosphodiesterase Inhibitor, Pentoxifylline"Bone. in press. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshimura,Y, Takaoka,K.: "Colocalization of Noggin and Bone Morphogenetic Protein-4 during Fracture Healing"J Bone Miner Res. in press. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshimura Y,Takaoka K: "Colocalization of Noggin and Bone Morphogenetic Protein-4 during Fracture Healing."Journal of Bone and Mineral Research. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Horiuchi H,Takaoka K: "Enhancement of Bone Morphogenetic Protein-2 Induced New Bone Formation in mice by a Phosphodiesterase Inhibitor, Pentoxifylline."Bone. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Saitou.N.,Takaoka K.: "A biodegradable polymer as a cytokine delivery system for inducing bone formation."Nature Biotechnology. 19(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kinoshita T,Takaoka K.: "Phosphodiesterase inhibitors,pentoxyfylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice."Bone. 27. 811-817 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawasaki S.,Takaoka K.: "The E-box motif, recognized by tissue-specific nuclear factor (s), is important for BMP-4 gene expression."Biochemical and Biophysical Research Communication.. 263. 560-565 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsutsumimoto T,Takaoka K.: "IL-1 and TNF-α suppress N-cadherin expression in MC3T3-E1 cells."Journal of Bone and Mineral Research. 14. 1751-1760 (1999)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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