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 …

R St-Arnaud, A Arabian, R Travers, F Barletta… - …, 2000 - academic.oup.com
R St-Arnaud, A Arabian, R Travers, F Barletta, M Raval-Pandya, K Chapin, J Depovere…
Endocrinology, 2000academic.oup.com
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 …
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.
Oxford University Press