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Role of Vitamin D hydroxylase on Bone Metabolism.

Research Project

Project/Area Number 12470392
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

SHINKI Toshimasa  Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (90138420)

Co-Investigator(Kenkyū-buntansha) KATAGIRI Takenobu  Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (80245802)
UDAGAWA Nobuyuki  Matsumoto dental University, School of Dentistry, Professor, 歯学部, 教授 (70245801)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥11,500,000 (Direct Cost: ¥11,500,000)
Keywords1α,25-dihydroxyvitamin D_3 / 24,25-dihydroxyvitamin D_3 / megalin / transgenic rat / 25-hydroxyvitamin D_3 / kidney / vitamin D binding protein / glomerulosclerosis / 単状糸球体腎炎
Research Abstract

Vitamin D is a steroid hormone that plays an important role in the maintenance of calcium and mineral metabolism. The 24-hydroxylase (CYP24) enzyme is a cytochrome P450 molecule that is distributed in the target tissues of vitamin D, and is induced specially by 1α, 25 dihydroxyvitamin D_3.Two functions of this enzyme have been revealed so far. One is production of 24, 25 dihydroxyvitamin D_3 from 25-hydroxyvitamin D_3 as a substrate. 24, 25-dihydroxyvitamin D_3 is known to have an effect on bone mass increments when high doses to rats. The other function of CYP24 is to inactivate 1α, 25 dihydroxyvitamin D_3 which strongly induces this enzyme, and to maintain vitamin D homeostasis. In order to clarify the physiological role of CYP24 in vivo, we have over expressed CYP24 in rats. In the present study we examined the mechanism for the alteration in serum vitamin D metabolites levels and analysed the consequent influences on bone metabolism. In CYP24 transgenic rat, we found Out that excessive alubuminures developed from early stages, and as albumin has an ability to bind megalin, a receptor for vitamin D-binding protein. The excretion of 25-hydroxyvitamin D3 in Tg rats increased as albumin excretion increased, and both parameters had a strong positive correlation. Finally we examined the influence of renal dysfunction on bone metabolism. There was a significant decrease in bone mineral density of Tg rats at 8 weeks of age when the serum parathyroid hormone level begins to rise. Infusion of 25-hydroxyvitamin D3 greatly increased the BMD in the tibia of Tg rats. The mechanisms of CYP24 overexpression for induction of nephritis need to be elucidated in future studies.

Report

(2 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Itoh, K., et al.: "Importance of membrane-or matrix-associated forms of m-CSF and RANKL/ODF in osteoclastogenesis by SaOS-4/3 cells expressing recombinant PTH/PTHrP receptors"J.Bone Miner.Res. 15・9. 1766-1775 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Udagawa, N. et al.: "Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function"Endocrinology. 141・9. 3478-3484 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang, X. et al.: "Effects of geranylgeranoic acid in bone : induction of osteoblast differentiation and inhibition of osteoclast formation"J.Bone Miner.Res.. 17・1. 91-100 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuno, H. et al.: "Rational Design, Synthesis and Biological Activity of Novel Conformationa11y Restricted Vitamin D Analogs, (22R)-and (22S)-22-Ethyl-1,25-dihydroxy-23,24-didehydro-24a,24b-dihomo-20-epivitamin D_3"J.Med.Chem.. 45(in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 新木 敏正: "メガリンとビタミンDの活性化"Annual Review 腎臓2002. 35-40 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 新木 敏正: "25-ヒドロキシビタミンD_3-1α-水酸化酵素の発現調節について"日本臨床. (製本中). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 新木 敏正: "カルシウムと骨"朝倉書店. 440 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 細金直文, 新木敏正: "新・分子骨代謝学と骨粗鬆症"メディカルレビュー社. 513 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh, K. et al: "Importance of membrane- or matrix-associated forms of m-CSF and RANKL/ODF in osteoclastogenesis by SaOS-4/3 cells expressing recombinant PTH/PTHrP receptors"J. Bone Miner. Res. 15: No.9. 1766-1775 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Udagawa, N.: "Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function."Endocrinology. 141:No.9. 3478-3484 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang, X et al: "Effects of geranylgeranoic acid in bone : induction of osteoblast differentiation and inhibition of osteoclast formation."J. Bone Miner. Res.. 17:No.1. 91-100 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuno, H. et al: "Rational design, synthesis and biological activity of novel conformationally restricted vitamin D analogs, (22R)- and (22S)-22-ethyl-l, 25dihydroxy-23, 24-di dehydro-24a, 24b-di homo-20-epivitamin D_3."J. Med. Chem. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh, K. et al.: "Importance of membrane-or matrix-associated forms of m-CSF and RANKL/ODF in osteoclastogenesis by SaOS-4/3 cells expressing recombinant PTH/PTHrP receptors"J. Bone Miner. Res. 15・9. 1766-1775 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Udagawa, N. et al.: "Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function"Endocrinology. 141・9. 3478-3484 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wang, X. et al.: "Effects of geranylgeranoic acid in bone : induction of osteoblast differentiation and inhibition of osteoclast formation"J. Bone Miner. Res.. 17・1. 91-100 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masuno, H. et al.: "Rational Design, Synthesis and Biological Activity of Novel Conformationally Restricted Vitamin D Analogs, (22R)-and (22S)-22-Ethyl-1, 25-dihydroxy-23, 24-didehydro-24a, 24b-dihomo-20-epivitamin D_3"J. Med. Chem.. 45(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 新木敏正: "メガリンとビタミンDの活性化"Annual Review 腎臓2002. 35-40 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 新木敏正: "25-ヒドロキシビタミンD_3-1α-水酸化酵素の発現調節について"日本臨床. (製本中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 新木敏正: "カルシウムと骨"朝倉書店. 440 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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