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Disorder of vitamin D metabolism in steroid-induced osteoporosis

Research Project

Project/Area Number 10470393
Research Category

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

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

Principal Investigator

HORIUCHI Noboru  Ohu University, Department of Biochemistry, Professor, 歯学部, 教授 (00107294)

Co-Investigator(Kenkyū-buntansha) MATSUNUMA Ayako  Ohu University, Department of Biochemistry, Research Associate, 歯学部, 助手 (30296040)
KAWANE Tetsuya  Ohu University, Department of Biochemistry, Research Associate, 歯学部, 助手 (00265208)
ABE Masatoshi  Ohu University, Department of Biochemistry, Lecturer, 歯学部, 講師 (10254872)
明野 ながこ  奥羽大学, 歯学部, 助手 (30231856)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2000: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
KeywordsOsteoporosis / Glucocorticoid / 1a-hydroxylase / 24-hydroxylase / Vitamin D receptor / Transcriptional regulation
Research Abstract

Glucocorticoid osteoporosis is the most common cause of drug-relate osteoporosis. Recent in vivo experiment showed that administration of glucocorticoids such as dexamethasone into mice markedly increased vitamin D-24-hydroxylase mRNA abundance and the enzyme activity in kidney. However, the regulation of 24-hydroxylase expression by dexamethasone has not been known in the bone, a target tissue of glucocorticoids. This study was undertaken to define the regulatory mechanism of dexamethasone on 24-hydroxylase gene expression in osteoblasts. Dexamethasone in the presence of 10^<-7>M 1α, 25-Dihydroxyvitamin D_3 [1,25 (OH)_2D_3] stimulated the 24-hydroxylase mRNA abundance and enzyme activity by UMR-106 osteoblast-like cells in a dose- and time-dependent fashion. Dexamethasone stimulation of 24-hydroxylase mRNA expression in UMR-106 cells was abrogated completely by pretreatment with cycloheximide, an inhibitor of protein synthesis, indicating that new protein synthesis is required for this stimulation. Northern blot analysis revealed that 10^<-6>M dexamethasone in the presence of 10^<-7>M 1,25 (OH)_2D_3 markedly increased in a transcription factor, c-fos, mRNA abundance. Other steroid hormones including corticosterone, cortisol, aldosterone, testosterone, estrogen and progesterone could not enhance 24-hydroxylase mRNA expression in UMR-106 cells. These results indicated that dexamethasone stimulated the 24-hydroxylase gene expression mediated through c-fos induction in the presence of 1,25 (OH)_2D_3 in osteoblasts.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Toyonobu Maeda: "Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells."Biochemical and Biophysical Research Communications. 280(3). 874-877 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masatoshi Abe: "Induction of collagenase-2 (matrix metalloproteinase-8) gene expression by interleukin-1β in human gingival fibroblasts."Journal of Periodontal Research. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagako Akeno: "Regulation of vitamin D-1α-hydroxylase and-24-hydroxylase expression by dexamethasone in mouse kidney."Journal of Endocrinology. 164(3). 339-348 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toyonobu Maeda: "Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells."Biochemical and Biophysical Research Communications. 280(3). 874-877 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masatoshi Abe: "Induction of collagenase-2 (matrix metalloproteinase-8) gene expression by interleukin- 1β in human gingival fibroblasts."Journal of Periodontal Research. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagako Akeno: "Regulation of vitamin D-1α-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney."Journal of Endocrinology. 164(3). 339-348 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tetsuya Kawane: "Insulin-like growth factor I suppresses parathyroid hormone (PTH)/PTH-related protein receptor expression via a mitogen-activated protein kinase pathway in UMR-106 osteoblast-like cells."Endocrinology. 140(2). 871-879 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Setsuo Hamada: "Regulation of small intestinal transit by central nervous calcitonin receptor."Hormone and Metabolic Research. 31(9). 499-504 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masatoshi Abe: "Inhibitory effects of 1,25-dihydroxyvitamin D_3 and 9-cis retinoic acid on parathyroid hormone-related protein expression by oral cancer cells (HSC-3)."Journal of Endocrinology. 156(2). 349-357 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagako Akeno: "Mouse vitamin D-24-hydroxylase : molecular cloning, tissue distribution, and transcriptional regulation by 1,25-dihydroxyvitamin D_3."Endocrinology. 138(6). 2233-2240 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tetsuya Kawane: "Starvation-induced increase in the parathyroid hormone/PTH-related protein receptor mRNA of bone and kidney in shamoperated and thyroparathyroidectomized rats."European Journal of Endocrinology. 137(3). 273-280 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toyonobu Maeda: "Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells."Biochemical and Biophysical Research Communications. 280(3). 874-877 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masatoshi Abe: "Induction of collagenase-2(matrix metalloproteinase-8) gene expression by interleukin-1β in human gingival fibroblasts."Journal of Periodontal Research. in press. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagako Akeno: "Regulation of vitamin D-1α-hydroxylase and-24-hydroxylase expression by dexamethasone in mouse kidney."Journal of Endocrinology. 164(3). 339-348 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Setsuo Hamada: "Regulation of small intestinal transit by central nervous calcitonin receptor"Hormone and Metabolic Research. 31. 499-504 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagako Akeno: "Regulation of vitamin D-1α-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney"Journal of Endocrinology. 164. 339-348 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagako Akeno: "Mouse vitamin D-24-hydroxylase:molecular cloning,tissue distribution,and transcriptional regulation by 1α,25-dihydroxyvitamin D_3." Endocrinology. 138. 2233-2240 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tetsuya Kawane: "Starvation-induced increase in the parathyroid hormone/PTH-related protein receptor mRNA of bone and kidney in sham-operated an thyroparathyroidectomized rats." European Journal of Endocrinology. 137. 273-280 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masatoshi Abe: "Inhibitory effects of 1,25-dihydroxyvitamin D_3 and 9-cis retinoic acid on prathyroid hormone-related protein expression by oral cancer cells(HSC-3)." Journal of Endocrinology. 156. 349-357 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tetsuya Kawane: "Insulin-like growth factor I suppresses parathyroid hormone(PTH)/PTH-related protein receptor expression via a mitogen-activated protein kinase pathway in UMR-106 osteoblast-like-cells." Endocrinology. 140. 871-879 (1999)

    • Related Report
      1998 Annual Research Report

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

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