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Acta Biomater:底物弹性模量通过β-连环蛋白转导调节脂肪来源的基质细胞向成骨和脂肪生成的分化

2018-08-24 MedSci MedSci原创

通常认为,间充质干细胞(MSCs)可因底物的生物物理特性而诱导分化成多个谱系。然而,使MSCs能够响应底物特性的确切的生物物理机制仍不清楚。 在目前的研究中,研究人员制备了具有不同硬度的聚二甲基硅氧烷(PDMS)基底,并探索了基质的弹性模量调节脂肪来源的基质细胞(ASCs)骨和脂肪形成的方式。最初,SEM检测显示,硬质和软质基质之间观察到细胞形态的变化。包括F-肌动蛋白的微丝和α-和β-微管

通常认为,间充质干细胞(MSCs)可因底物的生物物理特性而诱导分化成多个谱系。然而,使MSCs能够响应底物特性的确切的生物物理机制仍不清楚。

在目前的研究中,研究人员制备了具有不同硬度的聚二甲基硅氧烷(PDMS)基底,并探索了基质的弹性模量调节脂肪来源的基质细胞(ASCs)骨和脂肪形成的方式。最初,SEM检测显示,硬质和软质基质之间观察到细胞形态的变化。包括F-肌动蛋白的微丝和α-和β-微管蛋白的微管的细胞骨架染色进一步显示,硬基质上显示出更大的细胞扩散区域。然后,在硬基质上粘附分子与肌动蛋白细胞骨架连接的纽蛋白的表达增强。

粘着斑的这种变化进一步触发细胞内β-连环蛋白信号传导并促进其核转位,特别是在硬的底物上。β-连环蛋白信号传导对成骨谱系直接分化的影响是通过其下游蛋白Lef-1与成骨转录因子Runx2和Osx之间的直接结合,通过调节PPARγ的表达来分化成脂肪细胞谱系。刚度诱导的β-连环蛋白信号传导的不平衡最终诱导了刚性基质上较软基质上更强的成骨作用和更弱的脂肪形成。

综上所述,这项研究表明硬度对ASC分化的重要性,并有助于增加对机械传感,机械转导到干细胞分化的分子信号转导机制的理解。

原始出处:

Xie J, Zhang D, et al., Substrate elasticity regulates adipose-derived stromal cell differentiation towards osteogenesisand adipogenesis through β-catenin transduction. Acta Biomater. 2018 Aug 19. pii: S1742-7061(18)30485-9. doi: 10.1016/j.actbio.2018.08.018.

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    2018-08-29 windight
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    2018-11-30 sunylz
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    2018-08-26 zhaojie88
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    2018-08-24 131****1460

    学习了受益匪浅

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