Role of Mechanical Stimulations in Directing Mesenchymal Stem Cell Adipogenesis - The Mechanobiology of Obesity and Related Diseases - page 72

signaling regulation by compression and stretch. Compression upregulated
a-catenin, which is responsible for inactivating b-catenin required for osteogene-
sis. In contrast, b-catenin is upregulated by stretching and induces osteogenesis but
not chondrogenesis. The involvement of b-catenin in enhancing osteogenesis is
similar to that was observed for the stretch study to inhibit adipogenesis while
inducing osteogenesis [ 43 ].
Another study found that although dynamic compression or flow shear alone
was not able to induce chondrogenesis, the application of shear superimposed on
compression led to marked increases in chondrogenic gene expression [ 41 ]. Also,
a potential competition between compression and other environmental factor was
reported. For instance, a low oxygen environment was more stimulatory to
chondrogenesis than 1 h of dynamic compression [ 34 ]. Thus, although chondro-
genesis of MSCs can be stimulated by compression, there are other factors that are
sometimes more beneficial for increased chondrogenesis.
Studies regarding dynamic compression of MSCs yield varying results.
Although a few studies found osteogenesis to be the resulting lineage of MSCs that
were exposed to dynamic compression, chondrogenesis seems to be the more
likely fate. However, even chondrogenesis from MSCs experiencing dynamic
compression may be an unreliable fate if other conditions are not favorable. More
studies including environmental and soluble signals and also the other mechanical
modes may thus be required to clearly determine the effects of compression on
MSC fate decision. It is notable that some stretch studies demonstrated stretch may
overcome the regulation from soluble factors [ 10 ], while for the cell compression
not much information is available to date.
2.3 Effects of Fluid Shear
It is apparent that cell stretching and occasionally compression can support cellular
osteogenesis while inhibiting adipogenesis. Would fluid flow-induced shear,
another important mechanical signal in vivo, produce similar results? Again,
unlike cell stretch studies, not many reports have dealt with the fluid flow control
of adipogenesis. In the literature, as far as we know, there is no study testing the
effect of fluid flow on the adipogenesis of preadipocytes (e.g., 3T3-L1). However,
a few studies have examined the relative direction of MSC fate via fluid flow
toward osteogenesis and adipogenesis.
One study investigated the effects of oscillatory fluid flow on mesenchymal stem
cell osteogenesis, chondrogenesis, and adipogenesis by assessing the expression of
Runx2, Sox9, and PPARc, respectively [ 2 ]. In the absence of fluid flow, cell tension
signaling mediated MSC fate decision. For example, LPA (RhoA activator which
increases cytoskeletal tension) induced Runx2 upregulation but decreased PPARc
expression, and cytochalasin (actin disruptor) increased Sox9 and PPARc
expressions (Fig. 5 ). Interestingly, all three transcription factors responsible for
three lineages were upregulated due to fluid flow. Further, in the presence of