The vitamin D analog ZK191784 normalizes decreased bone matrix mineralization in mice lacking the calcium channel TRPV5
until further notice
SourceJournal of Cellular Physiology, 228, 2, (2013), pp. 402-407
Article / Letter to editor
Display more detailsDisplay less details
Journal of Cellular Physiology
SubjectNCMLS 3: Tissue engineering and pathology IGMD 9: Renal disorder; NCMLS 5: Membrane transport and intracellular motility IGMD 9: Renal disorder
Mice lacking the renal epithelial Ca(2+) channel TRPV5 (TRPV5(-/-)) display impaired renal Ca(2+) reabsorption, hypercalciuria, and intestinal Ca(2+) hyperabsorption, due to secondary hypervitaminosis D. Using these mice, we previously demonstrated that ZK191784 acts as an intestine-specific 1,25(OH)(2) D(3) antagonist without affecting serum calcium levels. On the other hand, it acted as an agonist in the kidney and the effects of ZK191784 on bone were ambiguous. The present study was undertaken to further evaluate the effect of the vitamin D receptor antagonist on murine bone in mice lacking TRPV5. Eight-week-old female Trpv5(+/+) and Trpv5(-/-) mice were treated for 4 weeks with or without 50 microg/kg/day ZK191784. Quantitative backscattered electron imaging showed that the reduced bone matrix mineralization found in femoral bones of Trpv5(-/-) mice was partially but significantly restored upon ZK191784 treatment, just as we observed for trabecular bone thickness. This supports the significance of 1,25(OH)(2) D(3) and optimal control of Ca(2+) homeostasis for bone formation and matrix mineralization. Restoration also took place at the bone gene expression level, where 1alpha-hydroxylase (Cyp27b1) mRNA in femurs from ZK-treated Trpv5(-/-) mice was upregulated compared to control levels. The downregulated 24-hydroxylase (Cyp24a1) gene expression in femoral bone indicated local vitamin D resistance in the mice treated with ZK191784. Phosphate homeostasis was unaffected between the groups as shown by unaltered serum PO(4)(3-) and fibroblast growth factor (FGF) 23 as well as Fgf23 mRNA expression in bone. In conclusion, circulating 1,25(OH)(2) D(3) is important for optimal control of Ca(2+) homeostasis but also for controlled bone formation and matrix mineralization.
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.