Trpv6 mediates intestinal calcium absorption during calcium restriction and contributes to bone homeostasis. Bone 2010 Aug;47(2):301-8
Date
04/20/2010Pubmed ID
20399919Pubmed Central ID
PMC2902603DOI
10.1016/j.bone.2010.04.595Scopus ID
2-s2.0-77955984248 (requires institutional sign-in at Scopus site) 90 CitationsAbstract
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. On 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 (approximately 1%) or low (approximately 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 aging 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.
Author List
Lieben L, Benn BS, Ajibade D, Stockmans I, Moermans K, Hediger MA, Peng JB, Christakos S, Bouillon R, Carmeliet GMESH terms used to index this publication - Major topics in bold
AgingAnimals
Bone Remodeling
Bone and Bones
Calcium
Calcium Channels
Calcium, Dietary
Duodenum
Gene Expression Profiling
Gene Expression Regulation
Homeostasis
Intestinal Absorption
Ion Channel Gating
Mice
Organ Size
Osteogenesis
Phosphates
RNA, Messenger
TRPV Cation Channels