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Evidence base treatment of renal osteodistropy

Research Project

Project/Area Number 17590066
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionNihon Pharmaceutical University

Principal Investigator

SHINKI Toshimasa  Nihon Pharmaceutical University, Professor, 薬学部, 教授 (90138420)

Co-Investigator(Kenkyū-buntansha) SAKURADA Chikai  Nihon Pharmaceutical University, Associate professor, 薬学部, 准教授 (30279244)
NAKAJIMA Takanori  Nihon Pharmaceutical University, Associate professor, 薬学部, 准教授 (80265404)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsKidney / Renal osteodystrophy / Vitamin D / Parathyroid hormone / Transgenic / Bone mineral / Vitamin D metabolism / Proteomics / 石灰化 / 骨吸収 / 副甲状腺 / カルシトニン / 腎炎 / 糖尿病
Research Abstract

24-Hydroxylase (CYP24) is an enzyme distributed in the target tissues of 1α,25-dihydroxyvitamin D_3 [1α,25(OH)_2D_3]. Two functions for this enzyme have been reported: One is production of 24,25-dihydroxyvitamin D_3 [24,25(OH)_2D_3] and the other is inactivation of 1α,25(OH)_2D_3. To elucidate other physiologic roles of CYP24 in vivo, we previously generated rats that constitutively express the CYP24 gene. These transgenic (Tg) rats developed unexpected phenotypes, such as low plasma levels of 24,25(OH)_2D_3, lipidemia, and albuminuria. In this study, we elucidated the mechanisms for inducing low plasma 24,25(OH)_2D_3 levels and bone loss. Tg rats excreted massive amounts of vitamin D binding protein (DBP), which coincided with the loss of albumin. In Tg rats, the renal expression pattern of megalin, which serves as an endocytotic receptor responsible for the reuptake of urinary proteins such as DBP and albumin, was identical to that of the wild-type rats. Excreted albumin appeared to compete for the binding and reabsorption of the DBP-25-hydroxyvitamin D_3 [25(OH)D_3] complex with megalin, resulting in a loss of 25(OH)D_3 into the urine and subsequent reduction of plasma 24,25(OH)_2D_3. In this prominent rat model of nephritis, supplementation of 25(OH)D_3 was effective in preventing bone loss in an early stage of renal insufficiency.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (14 results)

All 2007 2006

All Journal Article (11 results) Book (3 results)

  • [Journal Article] Involvement of Tiaml in apoptosis induced by bufalin in HeLa cells.2007

    • Author(s)
      Cao-Hong. et al.
    • Journal Title

      Anticancer. Res. 27・1A

      Pages: 245-249

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvemnet of Tiam1 in apoptosis induced by bufalin in HeLa cells.2007

    • Author(s)
      Cao-Hong. et al.
    • Journal Title

      anticancer. Res. 27・1A

      Pages: 245-249

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Analogs of 1α,25-dihydroxyvitamin D_3 with high potency in induction of osteoclastogenesis and prevention of dendritic cell differentiation : synthesis and biological evaluation of 2-substituted 19-norvitamin D analogs.2006

    • Author(s)
      Shimazaki, M. et al.
    • Journal Title

      Bioorg. Med. Chem. 14・13

      Pages: 4645-4656

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in osteoclasts.2006

    • Author(s)
      Woo J.T.et al.
    • Journal Title

      Proc. Natl. Acad. Sci. U S A. 103・12

      Pages: 4729-4734

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases.2006

    • Author(s)
      Aiba, I. et al.
    • Journal Title

      Steroids. 71・10

      Pages: 849-856

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Analogs of la,25-dihydroxyvitamin D3 with high potency in induction of osteoclastogenesis and prevention of dendritic cell differentiation : synthesis and biological evaluation of 2-substituted 19-norvitamin D analogs.2006

    • Author(s)
      Shimazaki, M.et al.
    • Journal Title

      Bioorg Med Chem 14(13)

      Pages: 4645-4656

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in osteoclasts.2006

    • Author(s)
      Woo J.T.et al.
    • Journal Title

      Proc Natl Acad Sci U S A. 103(12)

      Pages: 4729-4734

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases.2006

    • Author(s)
      Aiba, I. et al.
    • Journal Title

      Steroids 71(10)

      Pages: 849-856

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of Tiaml in apoptosis induced by bufalin in HeLa cells.2006

    • Author(s)
      Cao-Hong.et al.
    • Journal Title

      Anticancer Res 27(1A)

      Pages: 245-249

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in osteoclasts.2006

    • Author(s)
      Woo, J.T.et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 103(12)

      Pages: 4729-4734

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analogs of 1α,25-dihydroxyvitamin D_3 with high potency in induction of osteoclastogenesis and prevention of dendritic cell differentiation.2006

    • Author(s)
      Shimazaki, M.et al.
    • Journal Title

      Bioorg.Med.Chem. (in press)

    • Related Report
      2005 Annual Research Report
  • [Book] NEW生化学2006

    • Author(s)
      新木敏正 他
    • Total Pages
      537
    • Publisher
      廣川書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] NEW 生化学2006

    • Author(s)
      新木敏正 他
    • Total Pages
      537
    • Publisher
      廣川書店
    • Related Report
      2006 Annual Research Report
  • [Book] NEW 生化学2006

    • Author(s)
      新木敏正
    • Total Pages
      537
    • Publisher
      廣川書店
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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