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Basic study on the risk factors of osteoporosis.

Research Project

Project/Area Number 02454429
Research Category

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

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

Principal Investigator

SUDA Tatsuo  Showa Univ., School of Dentistry Professor, 歯学部, 教授 (90014034)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Naoyuki  Showa Univ., School of Dentistury Associate Professor, 歯学部, 助教授 (90119222)
TAKITO Jiro  Showa Univ., School of Dentistry Assistant, 歯学部, 助手 (00197237)
SHINKI Toshimasa  Showa Univ., School of Dentistry Lecturer, 歯学部, 講師 (90138420)
JIN Cheng He  Showa Univ., School of Dentistry Assistant, 歯学部, 助手 (10205049)
ABE Etsuko  Showa Univ., School of Dentistry Associate Professor, 歯学部, 助教授 (70119147)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1990: ¥5,800,000 (Direct Cost: ¥5,800,000)
Keywords1alpha, 25-Dihydroxyvitamin D_3 / Intestine epithelial cells / Osteoblasts / Osteoclasts / Calcium pump / the third component of complement (C3) / Bone resorbing agents / Growth factor / オステオポンチン / カルシウム吸収 / 小腸上皮細胞細胞 / ポリアミン / マクロファ-ジ / マクロファ-ジコロニ-刺激因子
Research Abstract

We referred osteoporosis to a general disease in abnormal calcium metabolism, and approached to clarify the regulation mechanism of calcium absorption in the intestine and the functions of osteotropic factors in bone formation and resorption. Results obtained in this study could be summarized as follows :
1. By comparing chick intestinal calcium absorption between brush border and basolateral membrane fractions which were purified by saccharide gradient centrifugation, the increased calcium absorption by 1alpha, 25-dihydroxyvitamin D_3 [1alpha, 25(OH)_2D_3] was much attributive to efflux of calcium from basolateral membranes than influx of calcium from brush border membranes. Several pieces of evidence supported that calcium pump present in the basolateral membranes was Ca^<2+>, Mg^<2+>-ATPase, which contributed to the intestinal calcium transport depending upon the phosphorylation-dephosphorylation forms.
2. A 190 kDa protein was purified from conditioned media of mouse bone marrow-derived stromal cell(ST2)and primary osteoblastic cell cultures treated with 1alpha, 25(OH)_2D_3 and identified as the third component of complement(C3). The regulation of C3 by 1alpha, 25(OH)_2D_3 was under a transcriptional level, and appeared to occur tissue-specifically. The production of C3 was increased by not only 1alpha, 25(OH)_2D_3, but also local bone-resorbing agents such as IL-1, TNFalpha, and LPS. Adding 1alpha, 25(OH)_2D_3 together with antibody against C3 to bone marrow cultures greatly inhibited the formation of TPAP-positive osteoclast-like multinucleated cells.
3. Macrophages were able to differentiate into osteoclast-like cells by culturing macrophages with ST2 cells in the presence of 1alpha, 25(OH)_2D_3 and dexamethasone. When the factor(s)committing osteoclast formation was examined, it was found that M-CSF is an important factor, which commits osteoclast progenitors differentiating into mature osteoclast cells.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Takito,J.: "Calcium uptake by brush-border and basolateral membrane vesicles in chick duodenum." Am.J.Physiol.258. G16-G23 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Udagawa,N.: "Origin of osteoclasts:Mature monocytes and macrophages are capable differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells." Proc.Natl.Acad.Sci.USA. 87. 7260-7264 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sato,T.: "The specific production of the third component of complement by osteobastic cells treated with 1α,25-dihydroxyvitamin D_3." FEBS Letters. 285. 21-24 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hong,M.H.: "Transcriptional regulation of the production of the third component of complement (C3) by 1α,25-dihydroxyvitamin D_3 in mouse marrow-derived stromal cells (ST2) and primary osteoblastic cells" Endocrinology. 129. 2774-2779 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takito,J.: "The mechanism of regulation of the calcium-pumping activity in chick intestine." Am.J.Physiol.,. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tanaka,S.: "The role of colony stimulating factors in osteoclast development:Macrophage colony-stimulating factor (M-CSF) is essential for differentiation rather than proliferation of osteoclast progenitors." (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Udagawa, N., et al.: "Origin of osteoclasts : Mature monocytes and macrophages are capable differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells." Proc. Natl. Acad. Sci. USA. 87. 7260-7264 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sato, T., et al.: "The specific production of the third component of complement by osteoblastic cells treated with 1alpha, 25-dihydroxyvitamin D_3." FEBS Letters. 285. 21-24 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Honh, M. H., et al.: "Transcriptional regulation of the production of the third component of complement (C3) by 1alpha, 25-dihydroxyitamin D_3 in mouse marrow-derived stromal cells (ST2) and primary osteoblastic cells." Endocrinology. 129. 2774-2449 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takito, J., et al.: "The mechanism of regulation of the calcium-pumping activity in chick intestine." Am. J. Physiol.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takito,J.: "Calcium uptake by brush-border and basolateral membrane vesicles in chick duodenum." Am.J.Physiol.258. G16-G23 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Udagawa,N.: "Origin of osteoclasts:Mature monocytes and macrophages are capable differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells." Proc.Natl.Acad.Sci.USA. 87. 7260-7264 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sato,T.: "The specific production of the third component of complement by osteoblastic cells treated with 1α,25-dihydroxyvitamin D_3." FEBS Letters. 285. 21-24 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hong,M.H.: "Transcriptional regulation of the production of the third component of complement (C3) by 1α,25-dihydroxyvitamin D_3 in mouse marrow-derived stromal cells (ST2) and primary osteoblastic cells" Endocrinology. 129. 2774-2779 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takito,J.: "The mechanism of regulation of the calcium-pumping activity in chick intestine." Am.J.Physiol.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tanaka,S.: "The role of colony stimulating factors in osteoclast development:Macrophage colony-stimulating factor (M-CSF) is essential for differentiation rather than proliferation of osteoclast progenitors." (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] SUDA,T.: "The role of vitamin D in bone and intestinal cell differentiation." Annu.Rev.Nutr.10. 195-211 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] TAKITO,J.: "Calcium uptake by brush border and basolateral membrane vesicles in chick duodenum." Am.J.Phsyiol.258. G16-G23 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] JIN,C.H.: "Interleukin 1 regulates the expression of osteopontin mRNA by osteoblasts." Mol.Cell.Endocrinol.74. 221-228 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] UDAGAWA,N.: "Origin of osteoclasts:Mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrowーderived stromal cell." Proc.Natl.Acad.Sci.USA. 87. 7260-7264 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] TANAKA,H.: "Transglutaminase is involved in the fusion of mouse alveolar macrophages induced by 1α,25ーdihydroxyvitamin D_3." Exp.cell Res.192. 165-172 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] SHINKI,T.: "Putrescine is involved in the vitamin D action in chick intestine." Gastroenterology. 100. 113-122 (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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