Lifelong challenge of calcium homeostasis in male mice lacking TRPV5 leads to changes in bone and calcium metabolism.
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.
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Bram C J
BC
van der Eerden
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
W Nadia H
WN
Koek
Ludwig Boltzman Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
Paul
P
Roschger
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
M Carola
MC
Zillikens
Department of Orthopedics, Erasmus MC, Rotterdam, The Netherlands.
Jan H
JH
Waarsing
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands.
Annemiete
A
van der Kemp
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Marijke
M
Schreuders-Koedam
Ludwig Boltzman Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
Nadja
N
Fratzl-Zelman
Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
Pieter J M
PJ
Leenen
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands.
Joost G J
JG
Hoenderop
Ludwig Boltzman Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
Klaus
K
Klaushofer
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands.
René J M
RJ
Bindels
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Johannes P T M
JP
van Leeuwen
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015519:Bone Density / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002113:Calcification, Physiologic / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000172:deficiency / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050916:TRPV Cation Channels / Q000172:deficiency / Q000378:metabolism*
D015220:Calcium Channels; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; D002118:Calcium
Gerotarget; TRPV5; aging; bone resorption; calcium homeostasis; mineralization