Research Papers: Gerotarget (Focus on Aging):
Lifelong challenge of calcium homeostasis in male mice lacking TRPV5 leads to changes in bone and calcium metabolism
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Bram C.J. van der Eerden1,*, W. Nadia H. Koek1,*, Paul Roschger2, M. Carola Zillikens1, Jan H. Waarsing3, Annemiete van der Kemp4, Marijke Schreuders-Koedam1, Nadja Fratzl-Zelman2, Pieter J.M. Leenen5, Joost G.J. Hoenderop4, Klaus Klaushofer2, René J.M. Bindels4 and Johannes P.T.M. van Leeuwen1
1 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
2 Ludwig Boltzman Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria
3 Department of Orthopedics, Erasmus MC, Rotterdam, The Netherlands
4 Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands
5 Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
* These authors have contributed equally to this paper
Bram C. J. van der Eerden, email:
Keywords: TRPV5, bone resorption, mineralization, calcium homeostasis, aging, Gerotarget
Received: January 05, 2016 Accepted: March 31, 2016 Published: April 18, 2016
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.
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