Role of Mechanical Stimulations in Directing Mesenchymal Stem Cell Adipogenesis - The Mechanobiology of Obesity and Related Diseases - page 65

Fig. 1 Cyclic mechanical stretch inhibits the adipogenesis of MSCs. a Lipid droplets were seen
on day 3 in unstretched control (CTL), which was increased by day 5. Cell stretching suppressed
this. b Effects of cell stretching on adipogenic (PPARc and adiponectin) gene expression (real-
time RT-PCR). Two types of media (multilineage potential 'M' and adipogenic 'A') were used.
The number 3 and 5 denote the day of culture. Statistics data are shown with 'a' for comparison
with M3 CTL (p \ 0.001) and 'b' for comparison between unstretched and stretched conditions
(p \ 0.05). Reprinted with permission from the Endocrine Society [ 43 ]
conditions are favorable for fat cell formation, but that strain also activates signals
that are crucial to MSC osteogenesis.
MSC adipogenesis may be inhibited when dynamic stretch is applied to the
cells. However, to what degree it can be influenced by the strain magnitude and the
rest period between each applied load is a question. In one study where low
intensity vibration (\10 microstrain, 90 Hz) and high magnitude strain (20,000
microstrain, 0.17 Hz) were examined, adipogenesis was suppressed when the cells
were subjected to 22 min bouts of either low intensity vibration or high magnitude
strain with at least a 1 h break between bouts [ 45 ]. When the 1 h break was
extended to 3 h, adipogenesis was suppressed even more. Therefore, it can be
concluded that cyclic stretch inhibition of MSC adipogenesis may be not only
dependent on the magnitude of the mechanical load, but is also dependent upon the
length of the refractory period between loads.
The cell stretch control of MSC adipogenesis may also depend on the stage of
MSC commitment and differentiation. In our recent study, we investigated the
effect of cell stretch on the MSC adipogenesis by applying cyclic stretch during the
MSC commitment stage (Fig. 2 ;[ 24 ]). We used the bone morphogenetic protein 4
(BMP4)-induced MSC adipogenesis model. BMPs were initially known for their
capacity to upregulate osteoblast differentiation and bone formation [ 9 ]. Addi-
tionally, BMPs regulate a variety of other developmental processes including the
developments of heart, central nervous system, and cartilage [ 1 ]. Interestingly, it