Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, PR China.
PLoS One. 2013 Apr 18;8(4):e61283. doi: 10.1371/journal.pone.0061283. Print 2013.
In native fibrocartilage, mechanotransduction allows the cells to perceive the physical microenvironment not only through topographical cues from the extracellular matrix, but also through mechanical cues, such as interstitial flow. To create a microenvironment that simultaneously integrates nanotopography and flow stimulus, we developed a biomimetic microfluidic device embedded with aligned nanofibers to contain microchambers of different angles, which enabled the flow direction to form different angles with the fibers. Using this device, we investigated the effects of microfluidic and nanotopographical environment on the morphology and fibrochondrogenesis of mesenchymal stem cells (MSCs) and the involvement of RhoA/ROCK pathway and Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ). The results showed that the flow direction perpendicular to aligned nanofibers was conducive to fibrochondrogenesis of MSCs. In addition, ROCK inhibitor and knockdown of YAP/TAZ disrupted fibrochondrogenic differentiation of MSCs. In conclusion, our data suggest the crucial role of mechanotransduction in regulating fibrochondrogenic differentiation of MSCs, which may be mediated by RhoA/ROCK pathway and YAP/TAZ.
在天然纤维软骨中，力学转导使细胞不仅能通过细胞外基质的形貌线索感知物理微环境，还能通过诸如间质流等力学线索感知。为了创造一个同时整合纳米形貌和流刺激的微环境，我们开发了一种仿生微流控装置，其中嵌入了排列整齐的纳米纤维，以容纳不同角度的微腔室，从而使流的方向与纤维形成不同的角度。使用该装置，我们研究了微流和纳米形貌环境对间充质干细胞（MSCs）形态和纤维软骨形成的影响，以及 RhoA/ROCK 通路和 Yes 相关蛋白（YAP）/含 PDZ 结合基序的转录共激活因子（TAZ）的参与。结果表明，与排列整齐的纳米纤维垂直的流方向有利于 MSCs 的纤维软骨形成。此外，ROCK 抑制剂和 YAP/TAZ 的敲低破坏了 MSCs 的纤维软骨分化。总之，我们的数据表明力学转导在调节 MSCs 的纤维软骨形成中起着关键作用，这可能是通过 RhoA/ROCK 通路和 YAP/TAZ 介导的。
