Evidence for tissue- and cell-type selective activation of the vitamin D receptor by Ro-26-9228, a noncalcemic analog of vitamin D3
Our recent studies have shown that the vitamin D analog Ro‐26‐9228 restores bone mineral density without inducing hypercalcemia in osteopenic rats. Our ex vivo experiments demonstrated that the analog upregulated gene expression in trabecular bone but not in the duodenum of female rats. We examined...
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Published in | Journal of cellular biochemistry Vol. 88; no. 2; pp. 267 - 273 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
New York
Wiley Subscription Services, Inc., A Wiley Company
01.02.2003
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Subjects | |
Online Access | Get full text |
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Summary: | Our recent studies have shown that the vitamin D analog Ro‐26‐9228 restores bone mineral density without inducing hypercalcemia in osteopenic rats. Our ex vivo experiments demonstrated that the analog upregulated gene expression in trabecular bone but not in the duodenum of female rats. We examined the mechanism for the tissue selectivity of Ro‐26‐9228 in Caco‐2, a human cell line of intestinal origin, and hFOB, and a human fetal osteoblast cell line. We found that the abilities of Ro‐26‐9228 and the natural hormone, 1,25‐dihydroxyvitamin D3 (1,25D3) to induce VDRE‐reporter gene expression in transiently transfected human osteoblasts are similar. In contrast, in Caco‐2 cells, Ro‐26‐9228 induces 40‐fold less reporter gene expression than 1,25D3 does. We also examined the abilities of the vitamin D receptor (VDR)‐ligand complexes from these two cell lines to interact with partners of transcription (glucocorticoid receptor‐interacting protein, VDR‐interacting protein, and retinoid X receptor), in pull‐down assays. These assays revealed that 1,25D3 induces similar levels of interaction of these co‐factors with VDR from both osteoblasts and intestinal cells. In contrast, Ro‐26‐9228 induces significant interaction of VDR from osteoblast cells with these co‐factors, but less of VDR from Caco‐2 cells. These results suggest that the cellular environment of intestinal cells, unlike that of osteoblasts, represses the ability of VDR‐Ro‐26‐9228 complexes to interact with transcription partners. J. Cell. Biochem. 88: 267–273, 2003. © 2002 Wiley‐Liss, Inc. |
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Bibliography: | istex:4E2BB539A349268A40B6F9399984A6C8D134647D ark:/67375/WNG-6ZTPG9NS-M ArticleID:JCB10344 National Institute of Health - No. DK 50583 (to S.P.) ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0730-2312 1097-4644 |
DOI: | 10.1002/jcb.10344 |