Effects of 1,25-dihydroxyvitamin D(3) on the local bone renin-angiotensin system in a murine model of glucocorticoid-induced osteoporosis.
Effects of 1,25-dihydroxyvitamin D(3) on the local bone renin-angiotensin system in a murine model of glucocorticoid-induced osteoporosis.
复制标题
1,25-二羟基维生素 D-3 对糖皮质激素诱导骨质疏松小鼠模型局部骨肾素-血管紧张素系统的影响
DOI：
10.3892/etm.2017.4404
复制
发表时间：
2017-06
影响因子：
2.7
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Shen L;Ma C;Shuai B;Yang Y
在实验动物模型和人体中，活性维生素D与循环中的肾素-血管紧张素系统（RAS）密切相关;然而，相应的局部骨数据仍然有限。本研究检测了在糖皮质激素诱导的骨质疏松症（GIOP）小鼠模型中补充1，25-二羟维生素D3是否改变了局部骨RAS元素。将36只8周龄小鼠随机分为三个相等大小的组：假手术组、GIOP组和1，25-二羟维生素D3治疗组。12周后，使用显微计算机断层扫描检查各组小鼠的第三腰椎和左侧股骨的松质骨显微结构。为了评估糖皮质激素使用的影响，评估了1，25-二羟维生素D3对松质骨微观结构、骨转换标志物表达、循环和主要RAS组分表达的影响。结果显示，治疗组和假手术组的骨体积分数、骨小梁数量和骨小梁厚度均显著高于GIOP组（P<0.05）。假手术组和治疗组的骨结构模型指数、骨小梁间距、骨表面积/骨体积比均显著低于GIOP组（P<0.05）。所有评估的参数在处理组和假手术组之间均未显示出显著差异。治疗组局部骨血管紧张素1型和2型受体及核因子-κB受体激活剂配体的mRNA表达水平显著低于GIOP组（P<0.05），而各组间循环蛋白水平无显著差异（P>0.05）。结论：1，25-二羟维生素D3可能通过下调GIOP小鼠局部骨RAS来调节骨代谢。
Active vitamin D is closely related to the circulating renin-angiotensin system (RAS) in experimental animal models and humans; however, corresponding local bone data remain limited. The present study examined whether 1,25-dihydroxyvitamin D3 supplementation altered local bone RAS elements in a murine model of glucocorticoid-induced osteoporosis (GIOP). A total of 36 8-week-old mice were randomized into three equal-sized groups: The sham, GIOP and 1,25-dihydroxyvitamin D3 treatment groups. After 12 weeks, the cancellous bone microstructure of the third lumbar vertebra and left femur from the mice from each group were examined using micro-computed tomography. To access the impact of glucocorticoid use, the effect of 1,25-dihydroxyvitamin D3 on cancellous bone microstructure, the expression of bone turnover markers, circulation and expression of the main RAS components was assessed. Results demonstrated that bone volume fraction, trabecular number and trabecular thickness of the treatment and sham groups were significantly higher than the GIOP group (P<0.05). Furthermore, the structure model index, trabecular separation and bone surface to bone volume ratio of the sham and treatment groups were significantly reduced compared with the GIOP group (P<0.05). All assessed parameters exhibited no significant differences between the treatment and sham groups. mRNA expression levels of local bone angiotensin type 1 and 2 receptors and receptor activator of nuclear factor-κB ligand were significantly lower in the treatment group than in the GIOP group (P<0.05); however, there were no significant differences in circulating protein levels between the groups (P>0.05). In conclusion, 1,25-dihydroxyvitamin D3 may modulate bone metabolism by downregulating the local bone RAS in mice with GIOP.