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首页> 外文期刊>Stem cells and development >Mesenchymal Stem Cell and Chondrocyte Fates in a Multishear Microdevice Are Regulated by Yes-Associated Protein
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Mesenchymal Stem Cell and Chondrocyte Fates in a Multishear Microdevice Are Regulated by Yes-Associated Protein

机译：在多剪切微设备中的间充质干细胞和软骨细胞的命运受是相关蛋白的调控。

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摘要

Mechanical cues exert considerable influence on the fates of stem cells and terminally differentiated chondrocytes. The elucidation of the interactions between cell fate and mechanical cues in nuclear mechanotransduction will provide new clues to modulate tissue homeostasis and regeneration. In this study, we used an integrated microfluidic perfusion device to simultaneously generate multiple-parameter fluid shear stresses to investigate the role of fluid flow stimuli in the regulation of Yes-associated protein (YAP) expression and the fates of mesenchymal stem cells (MSCs) and primary chondrocytes. YAP expression was regulated by the level of fluid flow stimulus in both MSCs and chondrocytes. An increase in the magnitude of stimulation enhanced the expression of YAP, ultimately resulting in an increase in osteogenesis and a decrease in adipogenesis for MSCs, and initiating dedifferentiation for chondrocytes. Cytochalasin D not only repressed nuclear YAP accumulation in the flow state, but also abrogated flow-induced effects on MSC differentiation and the chondrocyte phenotype, resulting in MSC adipogenesis and the maintenance of the chondrocyte phenotype. Our findings reveal the connection between YAP and MSC/chondrocyte fates in a fluid flow-induced mechanical microenvironment and provide new insights into the mechanisms by which mechanical cues regulate the fates of MSCs and chondrocytes.
机译：机械提示对干细胞和终末分化软骨细胞的命运有很大影响。阐明核机械转导中细胞命运与机械提示之间的相互作用将为调节组织动态平衡和再生提供新的线索。在这项研究中，我们使用集成的微流灌注设备同时生成多参数流体剪切应力，以研究流体刺激在调节Yes相关蛋白（YAP）表达和间充质干细胞（MSC）命运中的作用。和原代软骨细胞。 YAP表达受MSC和软骨细胞中流体流动刺激水平的调节。刺激幅度的增加会增强YAP的表达，最终导致MSC的成骨作用增加和成脂作用减少，并导致软骨细胞去分化。细胞松弛素D不仅抑制了流动状态下的核YAP积累，而且废除了流动诱导的对MSC分化和软骨细胞表型的影响，从而导致了MSC的成脂作用和软骨细胞表型的维持。我们的发现揭示了在流体流动诱导的机械微环境中，YAP与MSC /软骨细胞命运之间的联系，并为机械线索调节MSC和软骨细胞命运的机制提供了新见解。

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