| Lithocholic acid downregulates vitamin D effects in human osteoblasts. | |
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MedLine Citation:
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PMID: 20055894 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Osteoporosis is a common complication in chronic cholestasis. It has been proposed that retained substances such as bile acids may produce a damaging effect on bone cells. This study analyses the effects of lithocholic acid (LCA) on cell survival and vitamin D metabolism in human osteoblasts (hOB). MATERIALS AND METHODS: Human osteoblasts cultures were performed with or without foetal bovine serum (FBS) or human albumin (HA) at different LCA concentrations and times with or without vitamin D. RESULTS: Lithocholic acid at concentrations higher than 10(-5 )M decreased cell survival. This effect was partially prevented by the presence of FBS or HA. Vitamin D stimulated CYP24A, BGLAP and TNFSF11 expression in hOB and these effects were modified by nontoxic LCA concentrations. LCA significantly decreased vitamin D stimulation of CYP24A, BGLAP and TNFSF11 gene expression at 72%, 79% and 56% (respectively). LCA alone has an agonistic effect, as has vitamin D, thus partially increasing CYP24A and BGLAP expression, but with no changes on TNFRSF11B expression. Equivalent effects of the LCA were observed by performing gene reporter assays using MG-63 cells transfected with constructs containing CYP24A1 promoter regions. CONCLUSIONS: Lithocholic acid decreases the stimulatory effect of vitamin D on CYP24A, BGLAP and TNFSF11 expression in hOB. This effect is produced through vitamin D response elements (VDREs), located in the promoter regions of these genes, suggesting that LCA acts as a mild analogous of vitamin D, interacting with the vitamin D receptor. These results may explain the potential deleterious effects of retained bile acids on hOB. |
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Authors:
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S Ruiz-Gasp?; N Gua?abens; A Enjuanes; P Peris; A Martinez-Ferrer; M J Martinez de Osaba; B Gonzalez; L Alvarez; A Monegal; A Combalia; A Par?s |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of clinical investigation Volume: 40 ISSN: 1365-2362 ISO Abbreviation: Eur. J. Clin. Invest. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-08 Completed Date: 2010-05-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0245331 Medline TA: Eur J Clin Invest Country: England |
Other Details:
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Languages: eng Pagination: 25-34 Citation Subset: IM |
Affiliation:
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Centro de Investigaci?n Biom?dica en Red en Enfermedades Hep?ticas y Digestivas (CIBERehd), Barcelona, Spain. silvia.ruiz@ciberehd.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Survival Cells, Cultured Cholestasis / complications*, metabolism Down-Regulation Humans Lithocholic Acid / pharmacology* Osteoblasts / drug effects*, metabolism Osteocalcin / drug effects, metabolism Osteoporosis / genetics, metabolism* Osteoprotegerin / drug effects, metabolism Promoter Regions, Genetic / drug effects RANK Ligand / drug effects, metabolism RNA / genetics Steroid Hydroxylases / drug effects, metabolism Transfection Vitamin D / metabolism*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Osteoprotegerin; 0/RANK Ligand; 0/TNFRSF11B protein, human; 0/TNFSF11 protein, human; 104982-03-8/Osteocalcin; 1406-16-2/Vitamin D; 434-13-9/Lithocholic Acid; 63231-63-0/RNA; EC 1.14.-/Steroid Hydroxylases; EC 1.14.13.-/vitamin D 24-hydroxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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