title: Regulation of fibrochondrogenesis of mesenchymal stem cells in an integrated microfluidic platform embedded with biomimetic nanofibrous scaffolds.
abstract: 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.
authors: Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, PR China.
authors: Weiliang
authors: W
authors: Zhong
authors: Weiguo
authors: W
authors: Zhang
authors: Shouyu
authors: S
authors: Wang
authors: Jianhua
authors: J
authors: Qin
mesh_terms: D000217:Acyltransferases; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D032701:Biomimetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D020219:Chondrogenesis / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D008297:Male; D040542:Mechanotransduction, Cellular; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D057139:Nanofibers; D051381:Rats; D055758:SOX9 Transcription Factor / Q000096:biosynthesis; D014157:Transcription Factors / Q000502:physiology; D000091102:YAP-Signaling Proteins; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D050659:Core Binding Factor Alpha 1 Subunit; C493717:Runx2 protein, rat; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C509425:Yap1 protein, rat; D000217:Acyltransferases; C544439:Tafazzin protein, rat; D054460:rho-Associated Kinases
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