Abstract
Trpv5 plays an important role in calcium (Ca2+) homeostasis, among others by mediating renal calcium reabsorption. Accordingly, Trpv5 deficiency strongly stresses Ca2+ homeostasis in order to maintain stable serum Ca2+. We addressed the impact of lifelong challenge of calcium homeostasis on the bone phenotype of these mice.Aging significantly increased serum 1,25(OH)2D3 and PTH levels in both genotypes but they were more elevated in Trpv5−/− mice, whereas serum Ca2+ was not affected by age or genotype. Age-related changes in trabecular and cortical bone mass were accelerated in Trpv5−/− mice, including reduced trabecular and cortical bone thickness as well as reduced bone mineralization. No effect of Trpv5 deficiency on bone strength was observed. In 78-week-old mice no differences were observed between the genotypes regarding urinary deoxypyridinoline, osteoclast number, differentiation and activity as well as osteoclast precursor numbers, as assessed by flow cytometry.In conclusion, life-long challenge of Ca2+ homeostasis present in Trpv5−/− mice causes accelerated bone aging and a low cortical and trabecular bone mass phenotype. The phenotype of the Trpv5−/− mice suggests that maintenance of adequate circulatory Ca2+ levels in patients with disturbances in Ca2+ homeostasis should be a priority in order to prevent bone loss at older age.
Highlights
Maintenance of adequate Ca2+ levels is of crucial importance for many physiological processes in the body including neuronal excitability, muscle contraction and bone formation
In this study we aimed to investigate the bone phenotype of aging Trpv5+/+ and Trpv5-/- mice by detailed analyses of serum and urine parameters related to calcium homeostasis and bone resorption, bone microarchitecture, mineralization and strength in vivo
In 10-week-old Trpv5-/mice, both PTH and 1,25(OH)2D3 were at a level that is not reached before 52 weeks of age in Trpv5+/+ littermates (Figure 1 and Table 1)
Summary
Maintenance of adequate Ca2+ levels is of crucial importance for many physiological processes in the body including neuronal excitability, muscle contraction and bone formation. Bone is the major site of Ca2+ storage in the body, and formation and mineralization by osteoblasts as well as osteoclastic bone resorption, contribute to the maintenance of Ca2+ equilibrium in the circulation. Serum Ca2+ is tightly regulated through the concerted interactions of kidneys, intestines and bone. Transcellular Ca2+ (re) absorption is an important process in maintaining Ca2+ balance by these tissues [1, 2]. We published on the phenotype of mice lacking the epithelial Ca2+ channel Trpv (Trpv5-/-) [3]. TRPV5 is a Ca2+-selective transient receptor potential www.impactjournals.com/oncotarget
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