title: Mesenchymal stem cell and chondrocyte fates in a multishear microdevice are regulated by Yes-associated protein.
abstract: 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.
authors: Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, PR China.
authors: Weiliang
authors: W
authors: Zhong
authors: Kang
authors: K
authors: Tian
authors: Xifu
authors: X
authors: Zheng
authors: Linan
authors: L
authors: Li
authors: Weiguo
authors: W
authors: Zhang
authors: Shouyu
authors: S
authors: Wang
authors: Jianhua
authors: J
authors: Qin
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D005786:Gene Expression Regulation; D008297:Male; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D046210:Microfluidic Analytical Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D000091102:YAP-Signaling Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D000091102:YAP-Signaling Proteins; C509425:Yap1 protein, rat; D015638:Cytochalasin D