Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D.
Endocrinology
; 141(7): 2658-66, 2000 Jul.
Article
en En
| MEDLINE
| ID: mdl-10875271
ABSTRACT
The 25-hydroxyvitamin D-24-hydroxylase enzyme (24-OHase) is responsible for the catabolic breakdown of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of vitamin D. The 24-OHase enzyme can also act on the 25-hydroxyvitamin D substrate to generate 24,25-dihydroxyvitamin D, a metabolite whose physiological importance remains unclear. We report that mice with a targeted inactivating mutation of the 24-OHase gene had impaired 1,25(OH)2D catabolism. Surprisingly, complete absence of 24-OHase activity during development leads to impaired intramembranous bone mineralization. This phenotype was rescued by crossing the 24-OHase mutant mice to mice harboring a targeted mutation in the vitamin D receptor gene, confirming that the elevated 1,25(OH)2D levels, acting through the vitamin D receptor, were responsible for the observed accumulation of osteoid. Our results confirm the physiological importance of the 24-OHase enzyme for maintaining vitamin D homeostasis, and they reveal that 24,25-dihydroxyvitamin D is a dispensable metabolite during bone development.
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Base de datos:
MEDLINE
Asunto principal:
Esteroide Hidroxilasas
/
Calcitriol
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Densidad Ósea
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24,25-Dihidroxivitamina D 3
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Receptores de Calcitriol
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Sistema Enzimático del Citocromo P-450
Límite:
Animals
Idioma:
En
Revista:
Endocrinology
Año:
2000
Tipo del documento:
Article
País de afiliación:
Canadá