J Cell Mol Med:咪达唑仑通过外周苯二氮卓受体在人间充质干细胞中抑制软骨形成

2018-03-13 MedSci MedSci原创

咪达唑仑是一种苯二氮卓类衍生物,广泛用于镇静和手术。然而,既往研究表明,咪达唑仑在怀孕早期使用时与先天性畸形(如侏儒症)风险增加有关。最近的研究也表明咪达唑仑可抑制间充质干细胞(MSC)的成骨作用。 鉴于肥大软骨细胞可分化为成骨细胞和骨细胞并促成软骨内骨形成,咪达唑仑对软骨形成的作用尚不清楚。在这项研究中,我们应用人MSC细胞系KP细胞作为体外模型来研究咪达唑仑对软骨形成的影响。 首先

咪达唑仑是一种苯二氮卓类衍生物,广泛用于镇静和手术。然而,既往研究表明,咪达唑仑在怀孕早期使用时与先天性畸形(如侏儒症)风险增加有关。最近的研究也表明咪达唑仑可抑制间充质干细胞(MSC)的成骨作用。

鉴于肥大软骨细胞可分化为成骨细胞和骨细胞并促成软骨内骨形成,咪达唑仑对软骨形成的作用尚不清楚。在这项研究中,我们应用人MSC细胞系KP细胞作为体外模型来研究咪达唑仑对软骨形成的影响。

首先建立了一个体外软骨形成模型在微团培养或二维高密度培养,使用TGF-β驱动软骨诱导培养基。咪达唑仑的处理剂量依赖性地抑制软骨形成,使用阿尔新蓝染色的糖胺聚糖和软骨形成标志物,如SOX9和II型胶原蛋白的表达进行探究。

结果显示,外周苯二氮卓受体(PBR)拮抗剂PK11195或小干扰RNA对咪达唑仑的抑制拯救了咪达唑仑对软骨形成的抑制作用。另外,咪达唑仑抑制转化生长因子-β诱导的Smad3磷酸化,并且这种抑制作用可以用PBR拮抗剂PK11195拯救。

综上所述,该研究通过PBR为肌注骨骼系统的咪达唑仑诱导的先天性畸形提供了可能的解释。

原始出处:

Chen YC, Wu KC, et al., Midazolam inhibits chondrogenesis via peripheral benzodiazepine receptor in human mesenchymal stem cells. J Cell Mol Med. 2018 Mar 7. doi: 10.1111/jcmm.13584. [Epub ahead of print]

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    2018-09-30 维他命
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    2018-03-14 changjiu

    学习一下谢谢

    0

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    2018-03-13 清风拂面

    谢谢分享学习

    0

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    2018-03-13 1ddf0692m34(暂无匿称)

    学习了.涨知识

    0