Eur J Pharmacol:线粒体在甲基苯丙胺诱导的骨髓间充质干细胞成骨抑制中的作用

2018-03-15 MedSci MedSci原创

甲基苯丙胺(METH)滥用引起重大的身体、心理和社会问题。因此,在这项研究中,我们调查了它对骨髓间充质干细胞(MSCs)成骨分化的影响。结果发现METH呈剂量依赖性地影响MSCs的生存力。成骨诱导后,3和30μmol/l METH剂量对MSCs活力无影响,导致成骨标记基因(Alp、Bglap和Runx2)下调,RUNX2蛋白表达下降,ALP活性降低和矿化能力下降。线粒体在MSCs的成骨过程中是必不

甲基苯丙胺(METH)滥用引起重大的身体、心理和社会问题。因此,在这项研究中,我们调查了它对骨髓间充质干细胞(MSCs)成骨分化的影响。

结果发现METH呈剂量依赖性地影响MSCs的生存力。成骨诱导后,3和30μmol/l METH剂量对MSCs活力无影响,导致成骨标记基因(Alp、Bglap和Runx2)下调,RUNX2蛋白表达下降,ALP活性降低和矿化能力下降。

线粒体在MSCs的成骨过程中是必不可少的。我们对线粒体功能的分析表明,METH可降低ATP产量,抑制耗氧率,使线粒体膜电位去极化,但对呼吸链上五种复合物的蛋白表达无明显影响。此外,METH可能损害线粒体生物合成,如mtDNA减少和生物发生因子下调。线粒体融合调节因子在mRNA和蛋白水平也下降。然而,线粒体的分裂和线粒体自噬并未受到影响。

总之,我们的研究表明,接触METH可导致线粒体生物合成和融合以及线粒体功能障碍减少,因此抑制了MSCs的成骨作用。

原始出处:


Shen Y, Wu L, et al., The Role of Mitochondria in Methamphetamine-induced inhibitory effects on osteogenesis of Mesenchymal Stem Cells. Eur J Pharmacol. 2018 Mar 2;826:56-65. doi: 10.1016/j.ejphar.2018.02.049. [Epub ahead of print]

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    2018-05-14 yb6560
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    2018-03-17 zhaojie88