Abstract
Energy-dependent intestinal calcium absorption is important for the maintenance of calcium and bone homeostasis, especially when dietary calcium supply is restricted. The active form of vitamin D, 1,25-dihydroxyvitamin D
3
[1,25(OH)
2
D
3
], is a crucial regulator of this process and increases the expression of the transient receptor potential vanilloid 6 (
Trpv6
) calcium channel that mediates calcium transfer across the intestinal apical membrane. Genetic inactivation of
Trpv6
in mice (
Trpv6
−/−
) showed, however, that TRPV6 is redundant for intestinal calcium absorption when dietary calcium content is normal/high and passive diffusion likely contributes to maintain normal serum calcium levels. At the other hand,
Trpv6
inactivation impaired the increase in intestinal calcium transport following calcium restriction, however without resulting in hypocalcemia. A possible explanation is that normocalcemia is maintained at the expense of bone homeostasis, a hypothesis investigated in this study.
In this study, we thoroughly analyzed the bone phenotype of
Trpv6
−/−
mice receiving a normal (~ 1%) or low (~ 0.02%) calcium diet from weaning onwards using micro-computed tomography, histomorphometry and serum parameters.
When dietary supply of calcium is normal,
Trpv6
inactivation did not affect growth plate morphology, bone mass and remodeling parameters in young adult or ageing mice. Restricting dietary calcium had no effect on serum calcium levels and resulted in a comparable reduction in bone mass accrual in
Trpv6
+/+
and
Trpv6
−/−
mice (−35% and 45% respectively). This decrease in bone mass was associated with a similar increase in bone resorption, whereas serum osteocalcin levels and the amount of unmineralized bone matrix were only significantly increased in
Trpv6
−/−
mice.
Taken together, our findings indicate that TRPV6 contributes to intestinal calcium transport when dietary calcium supply is limited and in this condition indirectly regulates bone formation and/or mineralization.