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1997 Fiscal Year Final Research Report Summary

Establishment of assay systems for examining bone metabolism : Studies on differentiation and function of osteoblasts and osteoclasts

Research Project

Project/Area Number 07557118
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

TAKAHASHI Naoyuki  Showa University, School of Dentistry, Associate Professor, 歯学部, 教授 (90119222)

Co-Investigator(Kenkyū-buntansha) SASAKI Takehisa  Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (50129839)
YAMAGUCHI Akira  Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (00142430)
KATAGIRI Takenobu  Showa University, School of Dentistry, Assistant, 歯学部, 助手 (80245802)
UDAGAWA Nobuyuki  Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (70245801)
MIYAURA Chisato  Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (20138382)
Project Period (FY) 1995 – 1997
Keywordsosteoblast / myoblast / bone morphogenetic protein / Smad / osteoclast / bone resorbing factors / signal transduction / NF-kB
Research Abstract

We have established reliable assay systems for investigating signal transduction which is involved in differentiation and function of osteoblasts and osteoclasts. Following findings were obtained from a series of experiments using the assay systems.
Studies on Osteoblast Differentiation and Function
(1) We have studied the signal trensduction of bone morphogenetic protein 2 (BMP-2) in myoblastic C2C12 cells. C2C12 cells expressed type IA receptor (BMPR-IA) and type II (BMP-RII) for BMP-2, but not type IB receptor (BMPR-IB). (2) C2C12 cells transfected with a kinase domain-truncated BMPR-IA did not differentiate into ALP-positive cells even in the presence of BMP-2. (3) When activated mutant BMPR-IA and BMPR-IB were transfected into C2C12 cells, both mutated receptors induced ALP activity in the absence of BMP-2. (4) C2C12 cells expressed Smad1, Smad2, Smad4, Smad5 mRNAs, and the expression levels were not altered by treatment with BMP-2. When Smads were transfected into C2C12 cells, only … More Smad1 and Smad5 induced ALP activity. Transfection of Cterminal truncated Smad1 and Smad5 (dominant negative Smads) into C2C12 cells, which had been transfected with activated mutant BMPR-IB,induced ALP activity.
Studies on Osteoclast Differentiation and Function
(1) We established a method for obtaining functionally active osteoclasts from co-cultures of mouse osteoblastic cells and bone marrow cells. Signaling molecules such as phosphatidylinositol-3 kinase, tyrosine kinase, rho p21, and p130^<Cas> have been shown to be involved in ruffled border formation of osteoclasts. (2) Calcitonin and bisphosphonates inhibited osteoclast function through activation of protein kinase A and inhibition of tyrosine phosphatases, respectively. (3) Osteoblasts activated osteoclast function through a mechanism involving cell to cell contact. (4) IL-1 prevented spontaneous apoptosis of osteoclasts and enhanced their survival through activation of NF-kB.(5) The target cells of osteotropic hormones and cytokines such as 1alpha, 25 (OH)_2D_3, PTH and IL-11 in osteoclast formation in the co-culture are osteoblastic cells. Less

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Jimi, E., et al.: "Activation of NF-κB is involved in the survival of osteoclasts promoted by interleukin-1." J. Biol. Chem., in press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suda, T., et al.: "Regulation of osteoclast function." J. Bone Miner. Res.12. 869-879 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto, N., et al.: "Smad1 and Smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts." Biochem. Biophys. Res. Commun.238. 574-580 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akiyama, S., et al.: "Constitutively active BMP type I receptors transduce BMP-2 signals without the ligand in C2C12 myoblasts." Exp. Cell Res. 235. 362-369 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katagiri, T., et al.: "Bone morphogenetic protein-2 inhibits terminal differentiation of myogenic cells by suppressing the transcriptional of MyoD myogenin." Exp. Cell Res.230. 342-351 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyaura, C., et al.: "Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function." Proc. Natl. Acad. Sci. USA. 94. 9360-9365 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suda, T., et al.: "Vitamin D" Vitamin D and osteoclastogenesis., 20 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suda, T., et al.: "Principle of Bone Biology" Cells of boen : Osteoclast generation., 15 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jimi, E.et al.: "Activation of NF-kB is involved in the survival of osteoclasts promoted by interleukin-1." J.Biol.Chem.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suda, T.et al.: "Regulation of osteoclast function." J.Bone Miner.Res.12. 869-879 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto, N.et al.: "Smad1 and Smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts." Biochem.Biophys.Res Commun.238. 574-580 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akiyama, S.et al.: "Constitutively active BMP type I receptors transduce BMP-2 signals without the ligand suppressing the transcriptional activity of MyoD and myogenin." Exp.Cell Res.235. 362-369 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katagiri, T.et al.: "Bone morphogenetic protein-2 inhibits terminal differentiation of myogenic cells by suppressing the transcriptional activity of MyoD and myogenin." Exp.Cell Res.230. 342-351 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyaura, C.et al.: "lncreased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function." Proc.Natl.Acad.Sci.USA. 94. 9360-9365 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suda, T.et al.: "Vitamin D and osteoclastogenesis." Vitamin D. 219-339 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suda, T.et al.: "Cells of bone : Osteoclast generation" Principle of Bone Biology. 87-102 (1996)

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

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Published: 1999-03-16  

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