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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1988-11-14
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pubmed:abstractText |
The effects of three vitamin D3 metabolites, 25-hydroxyvitamin D3 (25-(OH)D3), 1 alpha,25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3), and 24R,25-dihydroxyvitamin D3 (24R,25-(OH)2D3) on the activity of alkaline phosphatase (AP), a key enzyme involved in biomineralization, have been studied in primary cultures of chicken epiphyseal growth plate chondrocytes. Dosages of 1 alpha, 25-(OH)2D3 (10(-12) to 10(-7) M) caused a progressive, dosage- and time-dependent decrease in cellular AP levels, IC50 occurring at approximately 10(-12) M. In contrast, 24R,25-(OH)2D3 at 10(-13) to 10(-10) M stimulated cellular AP activity, half-maximal stimulation occurring at about 10(-13) M. At higher levels (10(-10) to 10(-7) M), 24R,25-(OH)2D3 caused progressive reduction in AP activity. Maximal effects of 24R,25-(OH)2D3 were evident 48 h after administration of the metabolite. 25-(OH)D3 initially (24 h) caused a weak, dosage-dependent decrease in cellular AP activity, but after 48-72 h, low levels (10(-13) to 10(-11) M) caused a dosage-dependent increase in AP activity. Higher levels of 25-(OH)D (greater than 10(-10) M) were clearly inhibitory to AP. These findings reveal that the AP activity of growth plate chondrocytes is exquisitely sensitive to both 1 alpha,25- and 24R,25-(OH)2D3 but the response to each is in opposite directions. The paradoxical response of the cells to 25-(OH)D3 can be explained if the metabolite is slowly metabolized by a 24-hydroxylase to 24R,25-(OH)2D3 leading to stimulation of cellular AP.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/24,25-Dihydroxyvitamin D 3,
http://linkedlifedata.com/resource/pubmed/chemical/Alkaline Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/Calcifediol,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitriol,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydroxycholecalciferols
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0884-0431
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
1
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
489-95
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:3509742-24,25-Dihydroxyvitamin D 3,
pubmed-meshheading:3509742-Alkaline Phosphatase,
pubmed-meshheading:3509742-Animals,
pubmed-meshheading:3509742-Calcifediol,
pubmed-meshheading:3509742-Calcitriol,
pubmed-meshheading:3509742-Cells, Cultured,
pubmed-meshheading:3509742-Chickens,
pubmed-meshheading:3509742-Culture Media,
pubmed-meshheading:3509742-Dihydroxycholecalciferols,
pubmed-meshheading:3509742-Gene Expression Regulation,
pubmed-meshheading:3509742-Growth Plate,
pubmed-meshheading:3509742-Phenotype
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pubmed:year |
1986
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pubmed:articleTitle |
Effect of vitamin D metabolites on the expression of alkaline phosphatase activity by epiphyseal hypertrophic chondrocytes in primary cell culture.
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pubmed:affiliation |
Department of Chemistry, University of South Carolina, Columbia 29208.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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