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2002 Fiscal Year Final Research Report Summary

The Regulation of osteobiastogenesis and adipogenesis by BMP2

Research Project

Project/Area Number 12671804
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionOsaka University

Principal Investigator

NISHIMURA Riko  Osaka University Graduate School of Dentistry, Associate Professor, 歯学研究科, 助教授 (60294112)

Co-Investigator(Kenkyū-buntansha) HIRAGA Toru  Osaka University Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 講師 (70322170)
YONEDA Toshiyuki  Osaka University Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (80142313)
Project Period (FY) 2000 – 2002
KeywordsOsteoblast / Adipocytes / C / EBPβ / BMP2 / LIP / Cbfa1
Research Abstract

(1) Role of C/EBF beta in the differentiation of mesenchymal stem cells into osteoblasts and adipocytes
We found that C/EBP beta was expressed in mature osteoblasts as well as adipocytes, we, therefore, examined the role of C/EBP beta in osteoblastogenesis by overexpressing C/EBP beta using adenovirus technology. Overexpression of C/EBP beta able to induce the differentiation of mesenchymal stem cells into not only adipocytes but also osteoalasts. Furthermore, overexpression of C/EBP beta induced osteocalcin expression and transactivated osteocaicin promoter. The data indicated that C/EBP beta is an important transcription factor for osteoblast differentiation of mesenchymal cells.
(2) Cooperative role of C/EBP beta and Cbfal in osteoblast differentiation
We, next, evaluated the relationship between C/EBP beta and Cbfa1 that is a critical transcription factor in bone formation and osteoblastogenesis, and found that C/EBP beta physically associated with Cbfa1. More importantly, osteogenic action of Cbfa1 was further enhanced by overexpression of C/EBP beta, showing the important role of cooperation between C/EBP beta and Cbfa1 during osteoblast differentiation.
(3) Reciprocal role of C/EBP beta isoform, LIP, in osteoblastogenesis and adipogenesis
An isoform of C/EBP beta, LIP, was also expressed in mature osteoblasts, suggesting the role of LIP during osteoblastogenesis. Overexpression of LIP blocks the adipogenesis in a dominant-negative fashion, but exhibits osteogenic action as a co-factor for Cbfa1. Our data provide the new insight into the understanding the molecular mechanisms that determine the direction of mesenchymal stem cells in bone.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Hata K: "Differential Roles of Smad1 and p38 Kinase in the regulation of PPARγ during BMP2-induced Adipogenesis"Mol Biol Cell. 14. 545-555 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimura R: "Cbfa1 induces osteoblastic differentiation of C2C12 cells without interactions with Smad1 and Smad5"Bone. 31. 303-312 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhao M: "Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation"J Cell Biol.. 157. 1049-1060 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoneda T: "A Bone-Seeking Clone Exhibits Different Biological Properties from the MDA-MB-231 Parental Human Breast Cancer Cells and a Brain-seeking Clone In Vivo and In Vitro"J Bone Miner Res. 16. 1486-1495 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Michigami T: "Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and α4β1 integrin enhances production of osteoclast-stimulating activity in culture"Blood. 96. 1953-1960 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Marzia M: "Decreased c-Src expression enhances osteoblast differentiation and bone formation"J Cell Biol. 151. 311-320 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lai CF: "Transforming Growth Factor-beta Up-regulates the beta 5 Integrin Subunit Expression via Sp1 and Smad Signaling"J Biol Chem. 275. 36400-36406 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoneda T: "Actions of bisphosphonate on bone metastasis in animal models of breast cancer"Cancer. 88. 2979-2988 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lai CF, et al: "Transforming growth factor-beta up-regulates the beta 5 integrin subunit expression via Sp1 and Smad signaling."J Biol Chem. 275. 36400-36406 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mundy GR, et al: "Precllnical studies with zoledronic acid and other bisphosphonates: Impact on the bone microenvironment."Semin Oncol. 28(2, supp16). 35-44 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Cruz JC, et al.: "Ibandronate decreases bone disease development and osteoclast stimulatory activity in an in vivo model of human myeloma."Exp Hematol. 29. 441-447 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jackson JG, et al: "Regulation of breast cancer cell motility by insulin receptor substrate-2 (IRS-2) in metastatic variants of human breast cancer cell lines."Oncogene. 20. 7318-7325 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ji X, et al: "Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A."J Bone Miner Metab. 18. 132-139 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takaoka Y, et al: "The pancreas: A storehouse of protein anabolic factors and bone/calcium metabolism-regulating factors"J Bone Miner Metb. 18. 2-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoneda T: "Cellular and molecular basis of preferential metastasis of breast cancer to bone."J Orthop Sci. 5. 75-81 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoneda T, et al: "Actions of bisphosphonate on bone metastasis in animal models of breast cancer"Cancer. 88. 2979-2988 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jackson JG, et al: "Elevated levels of p66 Shc are found in breast cancer cell lines and primary tumors with high metastatic potential."Ciln Cancer Res. 6. 1135-1139 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Michigami T, et al: "Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and α4β1 integrin enhances production of osteoclast-stimulating activity in culture."Blood. 96. 1953-1960 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Marzia M, et al: "Decreased c-src expression enhances osteoblast differentiation and bone formation."J Cell Biol. 151. 311-320 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oyajobi BO, et al: "Therapeutic efficacy of a soluble RANK-IgG Fc (RANK. Fc) fusion protein in suppressing bone resorption and hypercalcemia in a model of humoral hypercalcemia of malignancy."Cancer Res. 61. 2572-2578 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiraga T, et al: "The bisphosphonate ibandronate promotes apoptosis in MDA-231 human breast cancer cells in bone metastases,"Cancer Res. 61. 4418-4424 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoneda T, et al: "A bone-seeking subclone exhibits different properties from the parental MDA-MB-231 human breast cancer cells and a brain-seeking subclone in vivo and in vitro."J Bone Miner Res. 16. 1486-1495 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhao M, et al: "Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation"J Cell Biol.. 157. 1049-1060 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimura R, et al: "Cbfa1 induces osteoblastic differentiation of C2C12 cells without interactions with Smad1 and Smad5."Bone. 31. 303-312 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ghosh-Choudhury N, et al: "Requirement of BMP-2-induced Phosphatidylinosito1 3-Kinase and Akt Serine/Threonine Kinase in Osteoblast Differentiation and Smad-dependent BMP-2 Gene Transcription"J Biol Chem. 277. 33361-33368 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hata K, et al: "Differential Roles of Smad1 and p38 Kinase in the regulation of PPARy during BMP2-induced Adipogenesis."Mol Biol Cell. 14. 545-555 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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