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Sex-related differences in the skeletal phenotype of aged vitamin D receptor global knockout mice.
J Steroid Biochem Mol Biol 2016; 164:361-368JS

Abstract

The role of the vitamin D receptor (VDR) in maintaining skeletal health appears to be complex and dependent on the physiological context. Global Vdr deletion in a mouse model (Vdr-/-) results in hypocalcemia, secondary hyperparathyroidism and bone features typical of vitamin D-dependent rickets type II. When weanling Vdr-/- mice are fed a diet containing high levels of calcium, phosphorus and lactose, termed the rescue diet, normalisation of serum calcium, phosphate and parathyroid hormone levels results in prevention of rickets at 10 weeks of age. However, 17 week old male Vdr-/- mice, fed the rescue diet, have been reported as osteopenic due to a decrease in bone formation when compared to wild type mice. We now report confirmation of this finding with further data on the effect of the rescue diet on appendicular and axial skeletal structures in male and female Vdr-/- mice at 26 weeks of age compared to Vdr+/- controls. All Vdr-/- mice were normocalcemic with no evidence of any mineralization defect. However, male Vdr-/- mice exhibited significantly reduced mineral in femoral and vertebral bones when compared to control littermate Vdr+/- mice, consistent with the previously reported data. In contrast, 26-week-old female Vdr-/- mice demonstrated significantly increased femoral trabecular bone volume although there was decreased vertebral trabecular bone volume, similar to males, and femoral cortical bone volume was unchanged. Thus, the Vdr-/- mouse model displays sex- and site-specific differences in skeletal structures with long-term feeding of a rescue diet. Although the global Vdr-/- ablation does not permit the determination of skeletal mechanisms producing these differences, these data confirm skeletal changes even when fed the rescue diet.

Authors+Show Affiliations

School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia.School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia.School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia.School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia.School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia.School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia.School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia,. Electronic address: howard.morris@unisa.edu.au.School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26690785

Citation

Ryan, Jackson W., et al. "Sex-related Differences in the Skeletal Phenotype of Aged Vitamin D Receptor Global Knockout Mice." The Journal of Steroid Biochemistry and Molecular Biology, vol. 164, 2016, pp. 361-368.
Ryan JW, Starczak Y, Tsangari H, et al. Sex-related differences in the skeletal phenotype of aged vitamin D receptor global knockout mice. J Steroid Biochem Mol Biol. 2016;164:361-368.
Ryan, J. W., Starczak, Y., Tsangari, H., Sawyer, R. K., Davey, R. A., Atkins, G. J., ... Anderson, P. H. (2016). Sex-related differences in the skeletal phenotype of aged vitamin D receptor global knockout mice. The Journal of Steroid Biochemistry and Molecular Biology, 164, pp. 361-368. doi:10.1016/j.jsbmb.2015.12.005.
Ryan JW, et al. Sex-related Differences in the Skeletal Phenotype of Aged Vitamin D Receptor Global Knockout Mice. J Steroid Biochem Mol Biol. 2016;164:361-368. PubMed PMID: 26690785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex-related differences in the skeletal phenotype of aged vitamin D receptor global knockout mice. AU - Ryan,Jackson W, AU - Starczak,Yolandi, AU - Tsangari,Helen, AU - Sawyer,Rebecca K, AU - Davey,Rachel A, AU - Atkins,Gerald J, AU - Morris,Howard A, AU - Anderson,Paul H, Y1 - 2015/12/09/ PY - 2015/06/11/received PY - 2015/11/09/revised PY - 2015/12/06/accepted PY - 2015/12/23/pubmed PY - 2017/6/15/medline PY - 2015/12/23/entrez KW - 1,25-Dihydroxyvitamin D(3) KW - Bone remodelling KW - Osteoblasts KW - Osteoclasts KW - Vitamin D receptor SP - 361 EP - 368 JF - The Journal of steroid biochemistry and molecular biology JO - J. Steroid Biochem. Mol. Biol. VL - 164 N2 - The role of the vitamin D receptor (VDR) in maintaining skeletal health appears to be complex and dependent on the physiological context. Global Vdr deletion in a mouse model (Vdr-/-) results in hypocalcemia, secondary hyperparathyroidism and bone features typical of vitamin D-dependent rickets type II. When weanling Vdr-/- mice are fed a diet containing high levels of calcium, phosphorus and lactose, termed the rescue diet, normalisation of serum calcium, phosphate and parathyroid hormone levels results in prevention of rickets at 10 weeks of age. However, 17 week old male Vdr-/- mice, fed the rescue diet, have been reported as osteopenic due to a decrease in bone formation when compared to wild type mice. We now report confirmation of this finding with further data on the effect of the rescue diet on appendicular and axial skeletal structures in male and female Vdr-/- mice at 26 weeks of age compared to Vdr+/- controls. All Vdr-/- mice were normocalcemic with no evidence of any mineralization defect. However, male Vdr-/- mice exhibited significantly reduced mineral in femoral and vertebral bones when compared to control littermate Vdr+/- mice, consistent with the previously reported data. In contrast, 26-week-old female Vdr-/- mice demonstrated significantly increased femoral trabecular bone volume although there was decreased vertebral trabecular bone volume, similar to males, and femoral cortical bone volume was unchanged. Thus, the Vdr-/- mouse model displays sex- and site-specific differences in skeletal structures with long-term feeding of a rescue diet. Although the global Vdr-/- ablation does not permit the determination of skeletal mechanisms producing these differences, these data confirm skeletal changes even when fed the rescue diet. SN - 1879-1220 UR - https://www.unboundmedicine.com/medline/citation/26690785/Sex_related_differences_in_the_skeletal_phenotype_of_aged_vitamin_D_receptor_global_knockout_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-0760(15)30150-3 DB - PRIME DP - Unbound Medicine ER -