Toxicology:研究揭示β-雌二醇拮抗咖啡因的负向调节骨稳态的作用

2017-12-01 MedSci MedSci原创

咖啡因负向调节骨质内稳态,导致骨质流失甚至骨质疏松,这种现象发生在雌激素缺乏的绝经后妇女身上,而不是健康的年轻女性。在这项研究中,我们确定了咖啡因对骨稳态的影响是否受到雌激素的拮抗作用及其机制。特别是在绝经后骨质疏松症女性中观察到高水平的cAMP(一种重要的第二信使),我们研究了cAMP在咖啡因对骨稳态影响中的作用。体内研究表明,咖啡因加速了骨质疏松大鼠的骨质流失,而β-雌二醇则削弱了咖啡因对骨骼

咖啡因负向调节骨质内稳态,导致骨质流失甚至骨质疏松,这种现象发生在雌激素缺乏的绝经后妇女身上,而不是健康的年轻女性。在这项研究中,我们确定了咖啡因对骨稳态的影响是否受到雌激素的拮抗作用及其机制。特别是在绝经后骨质疏松症女性中观察到高水平的cAMP(一种重要的第二信使),我们研究了cAMP在咖啡因对骨稳态影响中的作用。

体内研究表明,咖啡因加速了骨质疏松大鼠的骨质流失,而β-雌二醇则削弱了咖啡因对骨骼的负面影响。体外实验中,收集骨质疏松大鼠骨髓间充质干细胞(BMMSCs)。我们发现咖啡因和β-雌二醇对骨髓间充质干细胞的增殖、凋亡、成骨细胞分化、细胞外基质的合成和矿化存在相反的作用。使用成骨标记物的表达水平、碱性磷酸酶活性和茜素红染色评估这些参数。结果显示,咖啡因对BMMSCs的有害作用被β-雌二醇阻断。cAMP依赖性PKA途径参与调节咖啡因/β-雌二醇介导的细胞生长、存活和成骨。此外,敲除雌激素受体(ER)β后,β-雌二醇对咖啡因的拮抗作用几乎被消除。

综上所述,这些结果表明,通过与ERβ结合,β-雌二醇拮抗咖啡因对BMMSC中的细胞生长和成骨分化的负面影响是通过cAMP依赖性PKA信号传导通路发挥作用。

原始出处:

Wang C, Zhou Y, Guan X, Yu M, Wang H. β-Estradiol antagonizes the inhibitory effects of caffeine in BMMSCs via the ERβ-mediated cAMP-dependent PKA pathway. Toxicology. 2017 Nov 15;394:1-10. doi: 10.1016/j.tox.2017.11.015. 

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    2018-10-04 bugit
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    2018-11-08 changfy
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    2017-12-03 hxzhang