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Study on Interaction between Osteoclast Progenitors and Osteoblastic Cells in Osteoclast Development.

Research Project

Project/Area Number 03454437
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

TAKAHASHI Naoyuki  Showa Univ., School of Dentistry Associate Professor, 歯学部, 助教授 (90119222)

Co-Investigator(Kenkyū-buntansha) SASAKI Takahisa  Showa Univ., School of Dentistry Associate Professor, 歯学部, 助教授 (50129839)
TAKITO Jiro  Showa Univ., School of Dentistry Assistant, 歯学部, 助手 (00197237)
SUDA Tatsuo  Showa Univ., School of Dentistry Professor, 歯学部, 教授 (90014034)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1992: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1991: ¥3,200,000 (Direct Cost: ¥3,200,000)
Keywordsosteoclast / osteoblast / osteopetrosis / macrophage colony stimulating (M-CSF) / 1alpha,25(OH)_2D_3 / p60^<c-src> / ocマウス / M-CSF / c-src / マクロファ-ジコロニ-剌激因子 / MーCSF / 活性型ビタミンD / 骨吸収
Research Abstract

We have developed a co-culture system of mouse osteoblastic cells and spleen cells to investigate the interaction of osteoclast progenitors with osteoblastic cells in their differentiation into osteoclasts.Using this co-culture system, we examined [1] role of osteoblastic cells in osteoclast development, [2] pathogenesis of osteopetrotic disorders in op/op (osteopetrotic) and oc/oc (osteosclerotic) mutant mice, and [3] expression of p60^<c-src> (a product of c-src proto-oncogenen) in osteoclasts.
[1] Role of Osteoblastic Cells in Osteoclast Development The role of osteoblastic cells in osteoclast development was investigated in a co-culture system of mouse osteoblastic cells and spleen cells. We have shown that osteoblastic cells play an important role in modulating the differentiation of osteoclast progenitors through a mechanism of cell-to-cell interaction (5,6,8). The expression of an osteoclast-inducing factor (s) by osteoblastic cells appeared to be tightly regulated by bone-resorb … More ing factors such as 1alpha,25-dihydroxyvitamin D_3 and parathyroid hormone (1,2,6,11).
[2] Pathogenesis of Osteopetrotic Disorders in Mutant Mice We examined pathogenesis of osteopetrotic disorders in op/op and oc/oc mutant mice using a co-culture system of their osteoblastic cells and spleen cells. It was shown that osteoclast deficiency in op/op mice is due to a defect in osteoblastic cells, and that the M-CSF produced by osteoblastic cells plays a critical role in osteoclast development (3). We also found that M-CSF is indispensable for both proliferation of osteoclast progenitors and their differentiation into mature osteoclasts (4, 10). In experiments using oc/oc mice, we concluded that the lack of bone resorption in oc/oc mice is due to a defect of osteoclast progenitors, which fail to differentiate into functional osteoclasts in the microenvironment provided by osteoblastic cells (7).
[3] Expression of p60^<c-src> in Osteoclasts Recently, it was reported that the targeted disruption of c-src in mice induced osteopetrosis. We, therefore, examined expression of p60^<c-src> in authentic osteoclasts and osteoclast-like cells formed in the co-culture system. The expression of p60^<c-src> strikingly increased parallel with the appearance of osteoclast-like cells in the co-culture (9). The electron microscopic study revealed that p60^<c-src> was primarily localized on ruffled border membranes and vacuoles (9). These results indicate that p60^<c-src> is important in osteoclastic bone resorption. Less

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Takahashi,N.: "Deficiency of osteoclasts in osteoopetrotic (op/op) mice is due to a defect in the local microenvironment provided by osteoblastic cells." Endocrinology. 128. 1792-1796 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takahashi,N.: "Role of colony-stimulating factors in osteoclast development." J.Bone Miner. Res.6. 977-985 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Suda,T.: "Modulation of osteoclast differentiation." Endocrine Reviews. 13. 66-80 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tanaka,S.: "Osteoclasts express high levels of p60^<c-src>,preferentially on ruffled border membranes." FEBS Lett.313. 85-89 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Udagawa,N.: "Lack of bone resorption in osteosclerotic (oc/oc) mice is due to a defect in osteoclast progenitors rather than the local microenvironment provided by osteoblastic cells." Biochem.Biophys.Res.Commun.184. 67-72 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tanaka,S.: "Macrophage colony-stimulating factor (M-CSF) is indispensable for both proliferation and differentiation of osteoclast progenitors." J.Clin.Invest.91. 257-263 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeru Saito, et al.: "A stable analogue of throumboxane A_2, 9-11-epithio-11,12-methano-throumboxane A_2, stimulates bone resorption in vitro and osteo-clast-like cell formation in mouse marrow culture." Bone Miner.12. 15-20 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takuhiko Akatsu, et al.: "Role of prostaglandins in interleukin 1-induced bone resorption in mice in vitro." J. Bone Miner. Res.6. 183-190 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Naoyuki Takahashi, et al.: "Deficiency of osteoclasts in osteopetrotic mice is due to a defect in the local microenvironment provided by osteoblastic cells." Endocrinology. 128. 1792-1796 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Naoyuki Takahashi, et al.: "Role of colony stimulating factors in osteoclast development." J. Bone Miner. Res.6. 977-985 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tatsuo Suda, et al.: "Modulation of osteoclast differentiation." Endocrine Rev.13. 66-80 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tatsuo Suda, et al.: "The role of vitamin D in bone resorption." J. Cell Biochem.49. 53-58 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nobuyuki Udagawa, et al.: "Lack of bone resorption in osteosclerotic (oc/oc) mice is due to a defect in osteoclast progenitors rather than the local micro-environment provided by osteoblastic cells." Biochem. Biophys. Res. Commun.184. 67-72 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takuhiko Akatsu, et al.: "Preparation and characterization of a mouse multinucleated cell population." J. Bone Miner. Res.7. 1297-1306 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Sakae Tanaka, et al.: "Osteoclasts express high levels of p60^<c-src>, preferentially on ruffled forder membranes." FEBS Lett.313. 85-89 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Sakae Tanaka, et al.: "Macrophage colony-stimulating factor (M-CSF) is indispensable for both proliferation and differentiation of osteoclast progenitors." J. Clin. Invest.91. 257-263 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tatsuya Tamura, et al.: "A new resorption assay with mouse osteoclast-like multinucleated cells formed in vitro." J. Bone Miner. Res.(1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Suda,T.: "Modulation of osteoclast differentiation." Endocrine Reviews. 13. 66-80 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tanaka,S.: "Osteoclasts express high levels of p60^<c-src>,preferentially on ruffled border membranes." FEBS Left.313. 85-89 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Udagawa,N.: "Lack of bone resorption in osteosclerotic (oc/oc) mice is due to a defect in osteoclast progenitors rather than the local microenvironment provided by osteoblastic cells." Biochem.Biophys.Res.Commun.184. 67-72 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Akatsu,T.: "Preparation and characterization of a mouse osteoclast-like multinucleated cell population." J.Bone Miner.Res.7. 1297-1306 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tanaka,S.: "Macrophage colony-stimulating factor (M-CSF) is indispensable for both proliferation and differentiation of osteoclast progenitors." J.Clin.Invest.91. 257-263 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tamura,T.: "A new resorption assay with mouse osteoclast-like multinucleated cells formed in vitro." J.Bone Miner.Res.,. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Akatsu,T.: "Role of prostaglandins in interleukin 1-induced bone resorption in mice in vitro." J.Bone Miner.Res.6. 183-190 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takahashi,N.: "Deficiency of osteoclasts in osteopetrotic mice is due to a defect in the local microenvironment provided by osteoblastic cells." Endocrinology. 128. 1792-1796 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takahashi,N.: "Role of colony stimulating factors in osteoclast development." J.Bone Miner.Res.6. 977-985 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Suda,T.: "Modulation of osteoclast differentiation." Endocrine.Rev.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Suda,T.: "The role of vitamin D in boen resorption." J.Cell.Biochem.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sato,K.: "Prolonged decrease of serum calcium concentration by murine interferon-γ in hypercalcemic,human tumor (EC-GI)-bearing nude mice." Cancer Res.(1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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