QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rowling, M. J. Articles by Fleet, J. C. Search for Related Content PubMed PubMed Citation Articles by Rowling, M. J. Articles by Fleet, J. C.

---

Biochemical, Molecular, and Genetic Mechanisms

High Dietary Vitamin D Prevents Hypocalcemia and Osteomalacia in CYP27B1 Knockout Mice^1,2

³ Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556; and ⁴ Interdepartmental Nutrition Program and Department of Foods and Nutrition, Purdue University, West Lafayette, IN 47906

^* To whom correspondence should be addressed. E-mail: fleet{at}purdue.edu.

Mice lacking 25-hydroxycholecalciferol [25(OH)D]-1-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 µg), 10,000 (10K, 250 µg), or 20,000 (20K, 500 µg) 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.

This article has been cited by other articles:

				R. E. DE ANGEL, D. BERRIGAN, N. P. NUNEZ, S. D. HURSTING, and S. N. PERKINS Dietary Calcium Source Influences Body Composition, Glucose Metabolism and Hormone Levels in a Mouse Model of Postmenopausal Obesity In Vivo, July 1, 2009; 23(4): 527 - 535. [Abstract] [Full Text] [PDF]

				C. J. Narvaez, D. Matthews, E. Broun, M. Chan, and J. Welsh Lean Phenotype and Resistance to Diet-Induced Obesity in Vitamin D Receptor Knockout Mice Correlates with Induction of Uncoupling Protein-1 in White Adipose Tissue Endocrinology, February 1, 2009; 150(2): 651 - 661. [Abstract] [Full Text] [PDF]

				R. Bouillon, G. Carmeliet, L. Verlinden, E. van Etten, A. Verstuyf, H. F. Luderer, L. Lieben, C. Mathieu, and M. Demay Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice Endocr. Rev., October 1, 2008; 29(6): 726 - 776. [Abstract] [Full Text] [PDF]

				J. C. Fleet, C. Gliniak, Z. Zhang, Y. Xue, K. B. Smith, R. McCreedy, and S. A. Adedokun Serum Metabolite Profiles and Target Tissue Gene Expression Define the Effect of Cholecalciferol Intake on Calcium Metabolism in Rats and Mice J. Nutr., June 1, 2008; 138(6): 1114 - 1120. [Abstract] [Full Text] [PDF]