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2006 Fiscal Year Final Research Report Summary

Comprehensive analysis of bone formation and its application

Research Project

Project/Area Number 14104015
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Morphological basic dentistry
Research InstitutionTokyo Medical and Dental University (2004-2006)
Nagasaki University (2002-2003)

Principal Investigator

YAMAGUCHI Akira  Tokyo Medical and Dental University, Graduate School, Oral Pathology, Professor, 大学院医歯学総合研究科, 教授 (00142430)

Co-Investigator(Kenkyū-buntansha) KATSUBE Ken-ichi  Tokyo Medical and Dental University, Graduate School, Oral Pathology, Assistant Professor, 大学院医歯学総合研究科, 講師 (20233760)
SAKAMOTO Kei  Tokyo Medical and Dental University, Graduate School, Oral Pathology, Research Associate, 大学院医歯学総合研究科, 助手 (00302886)
TAMAMURA Sadahiro  Tokyo Medical and Dental University, Graduate School, Oral Pathology, Research Associate, 大学院医歯学総合研究科, 特任助手 (70431963)
Project Period (FY) 2002 – 2006
Keywordsosteoblast / Runx2 / CCN3 / Notch / Mesenchymal stem cell / frog / evolution / bone regeneration
Research Abstract

We investigate the following issues in this research. 1)Analyses of regulatory factors of osteoblast differentiation, 2)Establishment and characterization of mesenchymal stem cells, 3)Evolutional changes of skeletal tissues. Results in this study is as follow.
1)Analyses of regulatory factors of osteoblast differentiation
a)We established runx2-deficient cell lines, and demonstrate that osteoblast differentiation is induced by BMP-2 in these cells by using other transcription factors such as Dlx5 and Msx2. b)CCN3 (NOV) inhibits osteoblast differentiation by interacting with BMP and Notch signaling pathways. c)We revealed the important role of Msx2 in osteoblast differentiation.
2)Establishment and characterization of mesenchymal stem cells
a)We established mesenchymal stem cells from human hamartoma, and characterized their differentiation potencies into various mesenchymal cells, b)We established multipotent mesenchymal cell lines form human osteosarcoma cell lines, which exhibited differ … More entiation potential into osteoblasts, chondrocytes, and adipocytes, c)We investigated the differentiation potential of multipotent KUSA cells, which were isolated from murine bone marrow, and revealed that CCN3 inhibits osteoblast differentiation in this cell line.
3)Evolutional changes of skeletal tissues
a)We demonstrated that endochondral ossification is delayed prominently in frog long bones, compared with that in mammals. This was caused by the different expression profiles of Banded Hedgehog in frog, compared with expression profiles of Indian Hedgehog in mouse long bones. b)We established cell culture methods for muscle and chondrocytes isolated frogs. c)We compared the bone regeneration process between frog and mouse. Bone regeneration process was extremely delayed, compared with that of mouse. d)We investigated whether bones in frogs play important role in calcium reservoir, and suggested that the bones in frogs will not be involved in calcium reservoir.
These results will provide important information to establish new therapies for bone regeneration and osteoporosis. Less

  • Research Products

    (21 results)

All 2007 2006 2005 2004 2003

All Journal Article (21 results)

  • [Journal Article] BMP-2 promotes differentiation of osteoblasts and chondroblasts in Runx2-deficient cell lines.2007

    • Author(s)
      Liu T, Gao Y, Sakamoto K, Minamizato T, Furukawa K, Tsukazaki T, Shibata Y, Bessho K, Komori T, Yamaguchi A
    • Journal Title

      J Cell. Physiol 211

      Pages: 728-735

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways.2007

    • Author(s)
      Minamizato T, Sakamoto K, Liu T, KokubO H, Katsube K, Perbal B, Nakamura S, Yamaguchi A
    • Journal Title

      Biochem Biophys Res Commun 354

      Pages: 567-573

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulation of osteoclast differentiation and function by the CaMK/CREB pathway.2007

    • Author(s)
      Sato K, Suematsu A, Nakashima T, Takemoto- Kimura S, Aoki K, Morishita Y, Asahara H, Ohya K, Yamaguchi A, Takai T, Kodama T, Chatila TA, Bito H, Takayanagi H
    • Journal Title

      Nat Med 12

      Pages: 1410-1416

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction.2007

    • Author(s)
      Sato K, Okamoto K, Suematsu A, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H
    • Journal Title

      J Exp Med 203

      Pages: 2673-2682

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] BMP-2 promotes differentiation of osteoblasts and chondroblasts in Runx2-deficient cell lines.2007

    • Author(s)
      Liu T, Gao Y, Sakamoto K, Minamizato T, Furukawa K, Tsukazaki T, Shibata Y, Bessho K, Komori T, Yamaguchi A
    • Journal Title

      J Cell.Physiol 211

      Pages: 728-735

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways.2007

    • Author(s)
      Minamizato T, Sakamoto K, Liu T, Kokubo H, Kats be K, Per bal B, Nakamura S, Yamaguchi A
    • Journal Title

      Biochem Biophys Res Commun 354

      Pages: 567-573

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of osteoclast differentiation and function by the CaMK/CREB pathway.2007

    • Author(s)
      Sato K, Suematsu A, Nakashima T, Takemoto-Kimura S, Aoki K, Morishita Y, Asahara H, Ohya K, Yamaguchi A, Takai T, Kodama T, Chatila TA, Bito H, Takayanagi H
    • Journal Title

      Nat Med 12

      Pages: 1410-1416

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Modulation of mouse RANKL gene expression by Runx2 and PKA pathway.2006

    • Author(s)
      Mori K, Kitazawa R, Kondo T, Maeda S, Yamaguchi A, Kitazawa S
    • Journal Title

      J Cell Biochem 98

      Pages: 1629-1644

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Modulation of mouse RANKL gene expression by Runx2 and PKA pathway.2006

    • Author(s)
      Mori K, Kitazawa T, Kondo T, Maeda S, Yamaguchi A, Kitazawa S
    • Journal Title

      J Cell Biochem. 98

      Pages: 1629-1644

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] CCAAT/enhancer binding protein β isoform, LIP, regulates commitment of osteoblasts and adipocytes.2005

    • Author(s)
      Hata K, Nishimura R, Ueda M, Ikeda F, Matsubara T, Ichida F, Hisada K, Nokubi T, Yamaguchi A, Yoneda T
    • Journal Title

      Mol Cell Biol. 25

      Pages: 1971-1979

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression profile of Xenopus banded hedgehog, a homolog of mouse Indian hedgehog, is related to the late development of endochondral ossification in Xenopus laevis.2005

    • Author(s)
      Moriishi T, Shibata Y, Tsukazaki T, Yamaguchi A
    • Journal Title

      Biochem Biophys Res Commun 328

      Pages: 867-873

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Distinct roles of EGF repeats for the Notch signaling system.2005

    • Author(s)
      Sakamoto K, Wang SC, Katsube K, Yamaguchi A
    • Journal Title

      Exp Cell Res 302

      Pages: 281-291

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Critical regulation of BMP-induced osteoblastic differentiation by Deltal/Jaggedl-activated Notchl signaling.2005

    • Author(s)
      Nobta M, Tsukazaki T, Shibata Y, Chang X, Moriishi T, Sakano S, Shindo H, Yamaguchi A
    • Journal Title

      J Biol Chem 280

      Pages: 15842-15848

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Critical regulation of BMP-induced osteoblastic differentiation by Delta1/Jagged1-activated Notch1 signaling.2005

    • Author(s)
      Nobuta M, Tsukazaki T, Shibata Y, Chang X, Moriishi T, Sakano S, Shindo H, Yamaguchi A
    • Journal Title

      J Biol Chem 280

      Pages: 15842-15848

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Establishment of a clonal human mesenchymal cell line that retains multilineage differentiation capacity from a spinal hamartoma.2004

    • Author(s)
      Doiguchi Y, Tsukazaki T, Tomonag T, Nobuta M, Fujita S, Hayashi T, Nagai K, Matsumoto T, Shindo H, Yamaguchi A
    • Journal Title

      Cell Tissue Res 317

      Pages: 237-246

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Reciprocal roles of Msx2 in regulation of osteoblast and adipocyte differentiation.2004

    • Author(s)
      Ichida F, Nishimura R, Hata K, Matsubara T, Ikeda F, Hisada K, Yatani H, Cao X, Komori T, Yamaguchi A, Yoneda T
    • Journal Title

      J Biol Chem 279

      Pages: 34015-34022

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Isolation and characterization of a mesenchymal cell line that differentiates into osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice.2004

    • Author(s)
      Kadowaki A, Tsukazaki T, Hirata K, Shibata Y, Okubo Y, Bessho K, Komori T, Yoshida N, Yamaguchi A
    • Journal Title

      BONE 34

      Pages: 993-1003

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role of a new member of IGFBP superfamily, IGFBP-rP10, in proliferation and differentiation of osteoblastic cells.2004

    • Author(s)
      Shibata Y, Tsukazaki T, Hirata K, Cheng X, Yamaguchi A
    • Journal Title

      Biochem Biophys Res Commun 325

      Pages: 1194-1200

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Establishment of a clonal human mesenchymal cell line that retains multilineage differentiation capacity from a spinal hamartoma.2004

    • Author(s)
      Doiguchi Y, Tsukazaki T, Tomonaga T, Nobuta M, Fujita S, Hayashi T, Nagai K, Matsumoto T, Shindo H, Yamaguchi A
    • Journal Title

      Cell Tissue Res 317

      Pages: 237-246

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Isolation and characterization of a mesenchymal cell line that differentiates into osteoblasts in response to BMP-2 from calvariae GFP transgenic mice.2004

    • Author(s)
      Kadowaki A, Tsukazaki T, Yoshida N, Yamaguchi A
    • Journal Title

      BONE 34

      Pages: 993-1003

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Transplantation of skin fibroblasts expressing BMP-2 promotes bone repair more effectively than those expressing Runx2.2003

    • Author(s)
      Hirata K, Tsukazaki T, Kadowaki A, Furukawa K, Shibata Y, Moriishi T, Okubo Y, Bessho K, Komori T, Mizuno A, Yamaguchi A
    • Journal Title

      Bone 32

      Pages: 502-512

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

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Published: 2008-05-27  

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