Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption.
Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption.
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DOI：
10.1677/joe-10-0208
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Inoue S
中科院分区：
文献类型：
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作者：
Azuma K;Casey SC;Ito M;Urano T;Horie K;Ouchi Y;Kirchner S;Blumberg B;Inoue S
类固醇和异生物质受体（SXR）及其鼠直系同源物胆甾烷X受体（PXR）是主要在肝和肠中表达的核受体，它们在肝和肠中起异生物质传感器的作用。除了其作为异生素传感器的作用外，我们实验室和其他地方的先前研究已经确定了SXR/PXR作为骨稳态介导剂的作用。在这里，我们报告说，系统性删除PXR的结果在显着的骨量减少与机械脆性的雌性小鼠，年轻的4个月大。与野生型（WT）小鼠相比，PXR敲除（PXRKO）小鼠的骨密度（BMD）显著降低。股骨小梁骨的显微计算机断层扫描分析显示，与WT小鼠相比，PXRKO小鼠的三维骨体积分数显著降低。胫骨近端骨小梁的组织形态计量学分析显示PXRKO小鼠骨量显著减少。至于骨小梁的骨转换，在PXRKO小鼠中骨形成减少，而骨吸收增强。股骨皮质骨的组织形态计量学分析显示WT小鼠的皮质面积大于PXRKO小鼠。WT小鼠具有比PXRKO小鼠更厚的皮质宽度。三点弯曲试验表明，这些形态表型实际上导致了机械脆性。最后，与WT相比，PXRKO小鼠中磷酸盐、钙和碱性磷酸酶的血清水平没有变化。与我们以前的结果一致，我们得出结论，SXR/PXR促进骨形成和抑制骨吸收，从而巩固了SXR/PXR作为骨稳态的关键调节剂的作用。
The steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and intestine where they function as xenobiotic sensors. In addition to its role as a xenobiotic sensor, previous studies in our laboratories and elsewhere have identified a role for SXR/PXR as a mediator of bone homeostasis. Here, we report that systemic deletion of PXR results in marked osteopenia with mechanical fragility in female mice as young as 4 months old. Bone mineral density (BMD) of PXR knockout (PXRKO) mice was significantly decreased compared with the BMD of wild-type (WT) mice. Micro-computed tomography analysis of femoral trabecular bones revealed that the three-dimensional bone volume fraction of PXRKO mice was markedly reduced compared with that of WT mice. Histomorphometrical analysis of the trabecular bones in the proximal tibia showed a remarkable reduction in bone mass in PXRKO mice. As for bone turnover of the trabecular bones, bone formation is reduced, whereas bone resorption is enhanced in PXRKO mice. Histomorphometrical analysis of femoral cortical bones revealed a larger cortical area in WT mice than that in PXRKO mice. WT mice had a thicker cortical width than PXRKO mice. Three-point bending test revealed that these morphological phenotypes actually caused mechanical fragility. Lastly, serum levels of phosphate, calcium, and alkaline phosphatase were unchanged in PXRKO mice compared with WT. Consistent with our previous results, we conclude that SXR/PXR promotes bone formation and suppresses bone resorption thus cementing a role for SXR/PXR as a key regulator of bone homeostasis.