2000 Fiscal Year Final Research Report Summary
Disorder of vitamin D metabolism in steroid-induced osteoporosis
| Project/Area Number |
10470393
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Ohu University |
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Principal Investigator |
HORIUCHI Noboru Ohu University, Department of Biochemistry, Professor, 歯学部, 教授 (00107294)
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| 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)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Osteoporosis / Glucocorticoid / 1a-hydroxylase / 24-hydroxylase / Vitamin D receptor / Transcriptional regulation |
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| 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.
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