VDR haploinsufficiency impacts body composition and skeletal acquisition in a gender-specific manner.
VDR haploinsufficiency impacts body composition and skeletal acquisition in a gender-specific manner.
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DOI：
10.1007/s00223-011-9505-1
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发表时间：
2011-09
影响因子：
4.2
通讯作者：
Rosen, Clifford J.
中科院分区：
文献类型：
--
作者：
de Paula, Francisco J. A.;Dick-de-Paula, Ingrid;Bornstein, Sheila;Rostama, Bahman;Le, Phuong;Lotinun, Sutada;Baron, Roland;Rosen, Clifford J.
维生素D受体（VDR）对几乎所有维生素D的作用都至关重要，并且被认为是普遍表达的。我们假设VDR基因的一个等位基因的破坏会影响骨发育并产生代谢后果。将VDR杂合（VDR HET）小鼠的身体组成和骨量（BMD）与8周龄时雄性和雌性VDR KO和WT小鼠的身体组成和骨量进行比较。还在16周时评价雄性小鼠，并在VDR雌性小鼠中评价骨髓间充质干细胞（MSC）分化。此外，雌性VDR HET和WT小鼠接受间歇性PTH治疗或媒介物（VH）4周。在基线和治疗后测定BMD。给药结束时进行体内MRI检查;处死动物后进行μCT和骨组织形态计量学检查。VDR HET雄性小鼠在16周龄之前具有正常的骨骼发育，但显示出比WT小鼠显著更少的脂肪量增加。相反，雌性VDR HET小鼠在8周龄时显示全身BMD降低，但对PTH的骨骼反应正常。在VDR HET雌性小鼠中MSC分化也受损。因此，雌性VDR HET小鼠显示骨获取的早期损伤，而雄性VDR HET小鼠表现出瘦的表型。我们的研究结果表明，VDR HET小鼠是研究维生素D敏感性降低对代谢和骨骼影响的有用模型。
The vitamin D receptor (VDR) is crucial for virtually all of vitamin D’s actions and is thought to be ubiquitously expressed. We hypothesized that disruption of one allele of the VDR gene would impact bone development and would have metabolic consequences. Body composition and bone mass (BMD) in VDR heterozygous (VDR HET) mice were compared to those obtained in male and female VDR KO and WT mice at 8 weeks of age. Male mice were also evaluated at 16 weeks, and bone marrow mesenchymal stem cell (MSC) differentiation was evaluated in VDR female mice. Additionally, female VDR HET and WT mice received intermittent PTH treatment or vehicle (VH) for 4 weeks. BMD was determined at baseline and after treatment. MRI was done in vivo at the end of treatment; μCT and bone histomorphometry were performed after killing the animals. VDR HET male mice had normal skeletal development until 16 weeks of age but showed significantly less gain in fat mass than WT mice. In contrast, female VDR HET mice showed decreased total-body BMD at age 8 weeks but ad a normal skeletal response to PTH. MSC differentiation was also impaired in VDR HET female mice. Thus, female VDR HET mice show early impairment in bone acquisition, while male VDR HET mice exhibit a lean phenotype. Our results indicate that the VDR HET mouse is a useful model for studying the metabolic and skeletal impact of decreased vitamin D sensitivity.
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DOI：
10.1590/s0100-879x2006005000074
发表时间：
2007-04-01
影响因子：
2.3
作者：
Pereira, F.A.;Castro, J.A.S. de;Paula, F.J.A
通讯作者：
Paula, F.J.A
影响因子：
--
作者：
Erben, RG;Soegiarto, DW;Balling, R
通讯作者：
Balling, R
影响因子：
--
作者：
Melamed, Michal L.;Michos, Erin D.;Post, Wendy;Astor, Brad
通讯作者：
Astor, Brad
影响因子：
5.8
作者：
Adams, John S.;Hewison, Martin
通讯作者：
Hewison, Martin
影响因子：
6.2
作者：
Dardenne, O;Prud'Homme, J;St-Arnaud, R
通讯作者：
St-Arnaud, R