Role of Mechanical Stimulations in Directing Mesenchymal Stem Cell Adipogenesis - The Mechanobiology of Obesity and Related Diseases - page 64

For example, cell stretching induced FosB expression and other transcription
factors that indicate an increase in MSC osteogenesis [ 15 ]. A recent study showed
that uniaxial cyclic stretching at 10 % strain enhances the osteogenesis of MSCs
and adipose-derived stem cells (ADSCs) from normal donors and also from donors
with osteoporosis [ 7 ]. They showed that when MSCs from osteoporotic donors
were subjected to uniaxial stretching, genes associated with cell proliferation, bone
tissue development, and surprisingly angiogenesis were upregulated, suggesting
the role of cell stretch in facilitating MSC osteogenesis for bone formation com-
bined with blood supply.
Studies on MSC osteogenesis have also revealed the effects of stretch regimens
and the role of the differentiation potential of the cells to be stretched. Both
continuous (10 % strain, 1 Hz) and rest period-inserted (10 % strain, 1 Hz, 10 s
rest after each cycle) cyclic stretching were shown to have positive effects on the
osteogenesis of two human adipose-derived stem cells having different mineral
deposition potential [ 16 ]. They showed that the high calcium-depositing cell line
displayed a greater osteogenesis induction effect from the stretch stimulation. This
suggests that applying mechanical stretch to cell lines that are already more
inclined to produce bone may have a greater stimulatory effect. The magnitude of
strain is also important in directing MSC osteogenesis. When subjected to cyclic
stretching at 0.8-15 % strains (1 Hz), MSCs showed differential responses in
proliferation and differentiation. At 5, 10, and 15 % elongation, MSCs experienced
a significant increase in proliferation compared with cells without a mechanical
load [ 22 ]. On the other hand, alkaline phosphatase (AP) activity, a marker of early
stage MSC osteogenesis, increased significantly at 0.8 and 5 % strain, but
decreased at 10 and 15 %. Other osteogenic markers also indicated that osteo-
genesis may be stimulated by mechanical cell stretching only at low magnitudes of
strains.
Interestingly, studies have reported that an increase in MSC osteogenesis by
dynamic (cyclic) cell stretching is generally accompanied by a decrease in adi-
pogenesis. In a study using adipose mesenchymal stem cells cultured in both
normal and adipogenic medium, adipogenesis was inhibited by cyclic mechanical
stretch and osteogenesis was stimulated [ 54 ]. They observed that stretch induced
the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and
proposed that ERK activation may be involved in the mechanical stress-induced
trans-differentiation. Another study reported that even when mechanically-stret-
ched MSCs were exposed to adipogenic media conditions, they still entered
osteogenic lineage as assessed by Runx2 and osterix [ 43 ]. As shown in Fig. 1 ,
when 2 % cyclic strain was delivered for 6 h daily at 10 cycles/min, key adipo-
genic markers including peroxisome proliferator-activated receptor c (PPARc) and
adiponectin mRNA expressions were inhibited by 35 and 50 %, respectively, after
5 days. As a molecular mechanism, they proposed stretch-induced b-catenin sig-
naling (to maintain b-catenin level and activity) may play an important mediatory
role to inhibit the adipogenesis. Combined data support the idea that not only can
dynamic

(cyclic) mechanical stretch prevent MSC adipogenesis even when