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- Title
Mechanically Induced Focal Adhesion Assembly Amplifies Anti-Adipogenic Pathways in Mesenchymal Stem Cells.
- Authors
Sen, Buer; Guilluy, Christophe; Xie, Zhihui; Case, Natasha; Styner, Maya; Thomas, Jacob; Oguz, Ipek; Rubin, Clinton; Burridge, Keith; Rubin, Janet
- Abstract
The fate of pluripotent mesenchymal stem cells (MSC) is determined through integration of chemical, spatial, and physical signals. The suppression of MSC adipogenesis by mechanical stimuli, which requires Akt-induced inhibition of glycogen synthase kinase 3β (GSK3β) with β-catenin activation, can be enhanced by repetitive dosing within a single day. Here, we demonstrate that reapplication of cyclic strain within a 24-hour period leads to amplification of both Akt activation and its subsequent inhibition of GSK3β, such that total cycle number can be reduced while still inhibiting adipogenesis. Amplification of Akt signaling is facilitated by a dynamic restructuring of the cell in response to mechanical signals, as evidenced by a transient increase in focal adhesion (FA) number and increased RhoA activity. Preventing FA assembly or development of tension blocks activation of Akt by mechanical signals, but not by insulin. This indicates that the FA infrastructure is essential to the physical, but not necessarily the chemical, sensitivity, and responsiveness of the cell. Exploiting the transient nature of cytoskeletal remodeling may represent a process to enhance cell responsiveness to mechanical input and ultimately define the fate of MSCs with a minimal input. S TEM C ELLS 2011;29:1829-1836
- Subjects
PLURIPOTENT stem cells; GLYCOGEN synthase kinase-3; INSULIN; CELLULAR mechanics; CYTOSKELETON; CYTOSKELETAL proteins; CELL adhesion
- Publication
Stem Cells, 2011, Vol 29, Issue 11, p1829
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.732