Loading...
Please wait, while we are loading the content...
Similar Documents
High dietary vitamin D prevents hypocalcemia and osteomalacia in CYP27B1 knockout mice.
| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Rowling, Matthew J. Gliniak, Christy Welsh, JoEllen Fleet, James C. |
| Description | Country affiliation: United States Author Affiliation: Rowling MJ ( Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.) |
| Abstract | Mice lacking 25-hydroxycholecalciferol [25(OH)D]-1alpha-hydroxylase (CYP27B1) are growth retarded, hypocalcemic, and have poor bone mineralization. We tested whether high dietary cholecalciferol (VD3) could exert effects in the absence of CYP27B1 in vivo. Weanling male wild-type (WT) and CYP27B1 knockout (KO) mice were fed either a 2% calcium (Ca), 20% lactose rescue diet or an AIN93G diet (0.5% Ca, 0.4% phosphorus) containing 1000 (1K, the rodent requirement, 25 microg), 10,000 (10K, 250 microg), or 20,000 (20K, 500 microg) IU VD3/kg diet until 12 wk when blood and tissues were taken. Serum 25(OH)D was >90 nmol/L in the 1K diet group and increased >4-fold in mice fed 10K and 20K diets. The 1K diet impaired growth and caused hypocalcemia in KO mice; the 10K and 20K diets were as effective as the high Ca rescue diet in preventing these outcomes. High VD3 restored expression of vitamin D-regulated genes in intestine (calbindin D(9K)) and kidney (CYP27B1, 24-hydroxylase, calbindin D(9K)) of KO mice. Micro-computed tomography of femora revealed complete recovery of cortical bone in KO mice fed either the rescue or 10K diets but only partial recovery of trabecular bone measures (e.g. 40% lower bone volume, 20% lower trabecular thickness, and 23% increase in trabecular separation). These data show that very high serum 25(OH)D can influence Ca and bone metabolism independent of its conversion to 1,25 dihydroxycholecalciferol. However, neither high dietary Ca nor high dietary VD3 is sufficient to fully recover the phenotype of CYP27B1 KO mice. |
| File Format | HTM / HTML |
| ISSN | 00223166 |
| e-ISSN | 15416100 |
| Journal | Journal of Nutrition |
| Issue Number | 12 |
| Volume Number | 137 |
| Language | English |
| Publisher | American Society for Nutrition |
| Publisher Date | 2007-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Research Support, N.i.h., Extramural 25-hydroxyvitamin D3 1-alpha-hydroxylase Calcium, Dietary Prevention & Control Pharmacology Genetic Predisposition To Disease Mice, Knockout Animals Vitamin D Diet Aging Genetics Mice Discipline Nutrition Osteomalacia Hypocalcemia |
| Content Type | Text |
| Resource Type | Article |
| Subject | Nutrition and Dietetics Medicine |
