van der Eerden Bram C J, Koek W Nadia H, Roschger Paul, Zillikens M Carola, Waarsing Jan H, van der Kemp Annemiete, Schreuders-Koedam Marijke, Fratzl-Zelman Nadja, Leenen Pieter J M, Hoenderop Joost G J, Klaushofer Klaus, Bindels René J M, van Leeuwen Johannes P T M
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Ludwig Boltzman Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
Oncotarget. 2016 May 3;7(18):24928-41. doi: 10.18632/oncotarget.8779.
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.
瞬时受体电位香草酸亚型5（Trpv5）在钙（Ca2+）稳态中发挥着重要作用，其中包括介导肾脏对钙的重吸收。因此，Trpv5缺乏会强烈影响Ca2+稳态，以维持稳定的血清钙水平。我们研究了终身钙稳态挑战对这些小鼠骨骼表型的影响。衰老显著增加了两种基因型小鼠的血清1,25(OH)2D3和甲状旁腺激素（PTH）水平，但在Trpv5基因敲除（Trpv5-/-）小鼠中升高更为明显，而血清Ca2+不受年龄或基因型的影响。Trpv5-/-小鼠小梁骨和皮质骨质量的年龄相关变化加速，包括小梁骨和皮质骨厚度降低以及骨矿化减少。未观察到Trpv5缺乏对骨强度有影响。通过流式细胞术评估，在78周龄小鼠中，基因型之间在尿脱氧吡啶啉、破骨细胞数量、分化和活性以及破骨细胞前体细胞数量方面未观察到差异。总之，Trpv5-/-小鼠中存在的终身Ca2+稳态挑战导致骨骼衰老加速以及皮质骨和小梁骨低骨量表型。Trpv5-/-小鼠的表型表明，对于Ca2+稳态紊乱的患者，维持足够的循环Ca2+水平应成为预防老年骨质流失的首要任务。
