Trpv6 mediates intestinal calcium absorption during calcium restriction and contributes to bone homeostasis.
Trpv6 mediates intestinal calcium absorption during calcium restriction and contributes to bone homeostasis.
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DOI：
10.1016/j.bone.2010.04.595
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发表时间：
2010-08
期刊：
影响因子：
4.1
通讯作者：
Carmeliet, G.
中科院分区：
文献类型：
--
作者：
Lieben, L.;Benn, B. S.;Ajibade, D.;Stockmans, I.;Moermans, K.;Hediger, M. A.;Peng, J. B.;Christakos, S.;Bouillon, R.;Carmeliet, G.
能量依赖性肠钙吸收对维持钙和骨稳态很重要，特别是当饮食钙供应受到限制时。维生素D的活性形式1,25-二羟基维生素D3 [1,25(OH)2D3]是这一过程的关键调节剂，并增加瞬时受体电位香兰素6 （Trpv6）钙通道的表达，该通道介导钙在肠顶端膜上的转移。然而，小鼠Trpv6基因失活（Trpv6−/−）表明，当膳食钙含量正常/高时，Trpv6对肠道钙吸收是多余的，被动扩散可能有助于维持正常的血清钙水平。另一方面，Trpv6失活会损害限钙后肠道钙转运的增加，但不会导致低钙血症。一种可能的解释是正常钙血症的维持是以牺牲骨稳态为代价的，这是本研究的假设。在这项研究中，我们使用显微计算机断层扫描、组织形态测量和血清参数，彻底分析了从断奶开始接受正常（~ 1%）或低（~ 0.02%）钙饮食的Trpv6 - / -小鼠的骨表型。在膳食钙供应正常的情况下，Trpv6失活不影响青壮年或衰老小鼠的生长板形态、骨量和重塑参数。限制饮食钙对血清钙水平没有影响，并导致Trpv6+/+和Trpv6 - / -小鼠骨量累积减少（分别为- 35%和45%）。骨量的减少与骨吸收的增加相似，而血清骨钙素水平和未矿化骨基质的数量仅在Trpv6 - / -小鼠中显著增加。综上所述，我们的研究结果表明，当膳食钙供应有限时，TRPV6有助于肠道钙运输，并在这种情况下间接调节骨形成和/或矿化。
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 D3 [1,25(OH)2D3], 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.
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DOI：
10.1152/ajpgi.1998.274.2.g389
发表时间：
1998-02-01
影响因子：
4.5
作者：
Chirayath, MV;Gajdzik, L;Peterlik, M
通讯作者：
Peterlik, M
影响因子：
15.9
作者：
Maes, C;Coenegrachts, L;Carmeliet, G
通讯作者：
Carmeliet, G
影响因子：
15.9
作者：
Masuyama, Ritsuko;Stockmans, Ingrid;Carmeliet, Geert
通讯作者：
Carmeliet, Geert
影响因子：
4.1
作者：
Dardenne, O;Prud'homme, J;St-Arnaud, R
通讯作者：
St-Arnaud, R
影响因子：
4.8
作者：
Li, YC;Amling, M;Demay, MB
通讯作者：
Demay, MB