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Differentiation of Mesenchymal Stem Cells in Bone Marrow

Research Project

Project/Area Number 12557082
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Hematology
Research InstitutionKeio University (2002)
Kumamoto University (2000-2001)

Principal Investigator

SUDA Toshio  Keio University. School of Medicine, Professor, 医学部, 教授 (60118453)

Co-Investigator(Kenkyū-buntansha) HIRAO Atsushi  Keio University, School of Medicine, Assistant Professor, 医学部, 助手 (90343350)
OHBO Kazuyuki  Keio University, School of Medicine, Assistant Professor, 医学部, 助手 (70250751)
OIKE Yuichi  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (90312321)
大根田 修  熊本大学, 発生医学研究センター, 助手 (30311872)
高倉 伸幸  熊本大学, 発生医学研究センター, 助教授 (80291954)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2002: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥6,200,000 (Direct Cost: ¥6,200,000)
Keywordsosteoblast / osteoclast / RANK / ALCAM / mesenchymal stem cell / perichondrium / vascular invasion / ephrin-B2 / 造血幹細胞 / アンジオポエチンファミリー / 血管新生 / 骨髄間葉組織 / Side Population / ALCAM接着分子 / 造骨・破骨 / 造血環境 / 骨髄造血 / RANK / アンジオポエチン / ARPs
Research Abstract

We studied the linkage among osteogenesis, angiogenesis and hematopoiesis in bone marrow formation. Interaction between osteoclasts and osteoblasts is indispensable to form bone and bone cavity as hematopoietic tissues. RANK/RANKL provided new insights into the osteoclast differentiation pathway. We have established a pure osteoclast culture system by isolating precursor cells and cultured in the presence of M-CSF and soluble RANKL. This system revealed that differentiation of osteoclasts is anchorage-dependent and that osteoclastogenesis is completely inhibited by GM-CSF and switched to dendritic cell differentiation by suppression of c-Fos expression. On the other hand, we purified mesenchymal stem cells from perichondrial cells and characterized their differentiation. We show that chondrocytes inhibited the growth of vascular endothelial cells. Eph-ephrin signaling might be involved in the invasion of vascular cells. Now, we are trying to isolate osteoclast-specific molecules by DNA subtraction method between osteoclasts and macrophages derived from common precursor cells. Since these two types of cells express quite similar molecules, osteoclast-specific molecules are enriched. These osteoclast-specific molecules are targets to regulate the osteoclast function.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Miyamoto T: "An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor κB ligand"Blood. 96. 4335-4343 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto T: "Bifurcation of osteoclasts and dendritic cells from common progenitors"Blood. 98. 2544-2554 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nosaka K: "Mechanism of hypercalcemia in adult T-cell leukemia : overexpression of receptor activator of nuclear factor κB ligand on adult T-cell leukemia cells"Blood. 99. 634-640 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oike Y: "Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells"Blood. 100. 1326-1333 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sekimoto T: "Effect of direct angiogenesis inhibition in rheumatoid arthritis using a soluble vascular endothelial growth factor 1 chimeric protein"J. Rheumatol.. 29. 240-245 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arai F: "Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation"J. Exp. Med.. 195. 1549-1563 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto T: "Differentiation and function of osteoclasts"The Keio Journal of Medicine. 52. 1-7 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto T: "An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear An adherent condition is required for formation of multinuclear osteoclaste in the presence macrophage colony-stimulating factor and receptor activator of nuclear factor kB ligand"Blood. 96. 4335-4343 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto T: "Bifurcation of osteoclasts and dendritic cells from common progenitors"Blood. 98. 2544-2554 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nnsaka K.: "Mechanism of hypercalcemia in adult T-cell leukemia: overexpression of receptor activator of nuclear factor kB ligand on adult T-cell leukemia cells"Blood. 99. 634-640 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oike Y: "Regulation of vasculogenesis and angiogenesis by EphB / ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells"Blood. 100. 1326-1333 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sekimoto T: "Effect of direct angiogenesis inhibition in rheumatoid arthritis using a soluble vascular endothelial growth factor receptor 1 chimeric protein"J. Rheumatol.. 29. 240-245 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arai F: "Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation"J.Exp.Med.. 195. 1549-1563 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto T: "Differentiation and function of osteoclasts"The Keio Journal of Medicine. 52. 1-7 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nosaka K et al.: "Increased RANK ligand expression on adult T-cell leukemia cells is the critical factor of hyper-calcemia"Blood. 99. 634-640 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oike Y et al.: "Regulation of vasculogenesis and angiogenesis by Eph/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells"Blood. 100. 1326-1333 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arai F et al.: "Mesenchymal stem cells in perichondrium express activated cell adhesion molecule and participate in bone formation."J. Exp. Med. 195. 1449-1563 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suenobu S et al.: "A role of ephB4 receptor and its ligand, ephrin-B2 in erythropoiesis"Biochem Biophys Res Comm. 293. 1124-1131 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hamada K et al.: "Distinct roles of ephrin-B2 forward and EphB4 reverse signaling in endothelial cells"Arterioscler Thromb Vasc Biol. 23(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohbo K et al.: "Identification and characterization of stem cells in pre-pubertal spermatogenesis"Dev. Biol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamada Y: "Exogenous clustered neuropillin-1 enhances vasculogenesis and angiogenesis"Blood. 97. 1671-1678 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Zhang X-Q: "Stromal cells expressing ephrin-B2 promote the growth and sprouting of ephrin-B2^+ endothelial cells"Blood. 98. 1028-1037 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohneda O: "ALCAM (CD166) : its role in hematopoietic and endothelial development"Blood. 98. 2134-2142 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyamoto T: "Bifurcation of osteoclasts and dendritic cells from common precursors"Blood. 98. 2544-2554 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suda T: "Role of hematopoietic stem cells in angiogenesis"Int J Haematol. 174. 266-271 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nomiyama H: "Organization of the chemokine genes in the human and mouse major clusters of CC and CXC chemokines : diversification between the two species"Genes and Immunity. 2. 110-113 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takakura N: "A role for hematopoietic cells in promoting angiogenesis."Cell. 102. 199-209 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohneda O: "WECHE : a novel hematopoietic regulatory factor."Immunity. 12. 141-150 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hamada K: "VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculo-angiogenesis and hematopoiesis."Blood. 96. 3793-3800 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyamoto T: "An adherent condition is required for formation of multinuclear osteoclasts in the presence of M-CSF and RANKL."Blood. 96. 4335-4343 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamada Y: "Exogenous clustered neuropilin-1 enhances vasculogenesis and angiogenesis."Blood. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zhang X-Q: "Stromal cells expressing ephrin-B2 promote the growth and sprouting of ephrin-B2^+ endothelial cells."Blood. (in press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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