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The roles of nuclear transcription factors in calcium homeostasis

Research Project

Project/Area Number 10307046
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) UDAGAWA Nobuyuki  Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (70245801)
TAKAHASHI Naoyuki  Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (90119222)
SHINKII Toshimasa  Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (90138420)
TAKAMI Masamichi  Showa University, School of Dentistry, Assistant, 歯学部, 助手 (80307058)
KATAGIRI Takenobu  Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (80245802)
秋山 修一  昭和大学, 歯学部, 講師 (70276591)
自見 英治郎  昭和大学, 歯学部, 助手 (40276598)
山口 朗  昭和大学, 歯学部, 助教授 (00142430)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥37,800,000 (Direct Cost: ¥37,800,000)
Fiscal Year 1999: ¥17,400,000 (Direct Cost: ¥17,400,000)
Fiscal Year 1998: ¥20,400,000 (Direct Cost: ¥20,400,000)
Keywordsparathyroid hormone / 1α,25-dihydroxyvitamin D3 / 1α-hydroxylase / osteoclast / ODF / OCIF / RANK / M-CSF / ビタミンD / カルシトニン / 腎臓 / ステロイドホルモン / カルシウム
Research Abstract

The physiologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], is a nuclear hormone with pleiotropic action on the control of calcium homeostasis and bone formation, induction of cellular differentiation and apoptosis, inhibition of cellular proliferation, and other cellular signaling processes. The actions of the hormone are mediated by the vitamin D receptor (VDR), a transcription factor that is a nuclear receptor for 1α,25(OH)2D3 and a member of the nuclear receptor superfamily.
A full-length cDNA for the rat kidney mitochondrial cytochrome P450 mixed function oxidase, 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1), was cloned from a vitamin D-deficient rat kidney cDNA library. The sequence analysis showed that CYP27B1 consisted of 2469 bp in length and contained an open reading frame encoding 501 amino acids. The expression of CYP27B1 mRNA was greatly increased in the kidney of hypocalcemic rats fed a low Ca diet. It is believed that the major regulator for … More renal CYP27B1 is parathyroid hormone (PTH) secreted in response to hypocalcemia. Administration of PTH into normocalcemic normal rats, however, did not induce at all renal expression of CYP27B1 mRNA. In contrast, a single injection of calcitonin (CT) dose- and time-dependently increased the expression of CYP27B1 mRNA in the kidney of normal rats. These results suggest that CT plays an important role in the maintenance of serum 1α,25(OH)2D3 under normocalcemic physiological conditions at least in rats.
Osteoclast differentiation factor (ODF), a novel member of the TNF ligand family, is expressed as a membrane-associated protein by osteoblasts/stromal cells. The soluble form of ODF (sODF) induces the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. A soluble form of RANK as well as osteoprotegerin/osteoclastogenesis inhibitory factor, a decoy receptor of ODF, blocked OGL formation and prevented the survival, multinucleation, and pit-forming activity of prefusion osteoclasts induced by sODF. These results suggest that ODF regulates not only osteoclast differentiation but also osteoclast function in mice through the receptor RANK. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Tsurikai, T., et al: "Role of macrophage colony-stimulating factor and osteoclast differentiation factor in osteociastogenessis"J. Bone Miner. Metab. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi, K., et al: "Tumor necrosis factor a stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction"J. Exp. Med.. 191. 275-286 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Udagawa, N., et al: "Osteoblasts/stromal cells stimulate osteoclast function through the expression of osteoclast differentiation factor but not macrophage colony-stimulating factor"Bone. 25. 517-523 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinki, T., et al: "Calcitonin is a major regulator for the expression of renal 25-hydroxyvitamin D3-1α-hydroxylase gene in normacalcemic rats"Proc. Netl. Acad. Sci USA. 96. 8253-8258 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kotake, S., et al: "IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis,"J. Clin. Invest. 103. 1345-1352 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Brenza H. L., et al.: "Parathyroid hormone activation of the 25-hydroxyvitamin D3-1a-hydroxylase gene promoter."Proc. Netl. Acad. Sci. USA. 95. 1387-1391 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsurukai, T. et al.: "Role of macrophage colony-stimulating factor and osteoclast differentiation factor in osteoclastogenesis"J. Bone Miner. Metab. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi, K. et al.: "Tumor necrosis factor a stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction"J. Exp. Med.. 191. 275-286 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Udagawa, N. et al.: "Osteoblasts/stromal cells stimulate osteoclast function through the expression of osteoclast differentiation factor but not macrophage colony-stimulating factor."Bone. 25. 517-523 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinki, T. et al.: "Calcitonin is a major regulator for the expression of renal 25-hydroxyvitamin D3-la-hydroxylase gene in normocalcemic rats."Proc. Natl. Acad. Sci. USA. 96. 8253-8258 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kotake, S. et al.: "IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis."J. Clin. Invest. 103. 1999. 1352 (1345)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Brenza, H.L. et al.: "Parathyroid hormone activation of the 25-hydroxyvitamin D3-1 a-hydroxylase gene promoter."Proc. Natl. Acad. Sci. USA. 95. 1387-1391 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsurukai,T.,et al.: "Role of macrophage colony-stimulating factor and osteoclast differentiation factor in osteoclastogenesis."J.Bone Miner.Metab.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kobayashi,K.,et al.: "Tumor necrosis factor a stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction."J.Exp.Med.. 191. 275-286 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasuda,H.,et al.: "A novel molecular mechanism modulating osteoclast differentiation and function."Bone. 25. 109-113 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Udagawa,N.,et al.: "Osteoblasts/stromal cells stimulate osteoclast function through the expression of osteoclast differentiation factor but not macrophage colony-stimulating factor."Bone. 25. 517-523 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shinki,T., et al.: "Calcitonin is a major regulator for the expression of renal 25-hydroxyvitamin D3-1α-hydoroxylase gene in normocalcemic rats."Proc.Netl.Acad.Sci.USA. 96. 8253-8258 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamamoto,K.,et al.: "Three-dimensional structure-function relationship of vitamin D:side chain location and various activities."Bioorg.Med.Chem.Lett.. 9. 1041-1046 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suda,T.,et al.: "Modulation of osteoclast differentation and function by osteoblasts/stromal cells." Endocrine Rev.in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshida,T.,et al.: "Two novel 1 α-hydroxylase mutations in french-canadians with vitamin D dependency rickets type II." Kidney Int.54. 1437-1443 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Brenza,HL.,et al.: "Parathyroid hormone activation of the 25-hydroxyvitamin D_3-1 α-hydroxylase gene promoter." Proc.Natl.Acad.Sci.USA. 95. 1387-1391 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shinki,T.,et al.: "Cloning and expression of rat 25-hydroxyvitamin D_3-1 α-hydroxylase cDNA." Proc.Natl.Acad.Sci.USA. 94. 12920-12925 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Monkawa,T.,et al.: "Molecular cloning of cDNA and genomic DNA for human 25-hydroxyvitamin D_3 1 α-hydroxylase." Biochem.Biophys.Res.Commun.239. 527-533 (1997)

    • Related Report
      1998 Annual Research Report
  • [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)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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