Mechanical Stretching and Signaling Pathways in Adipogenesis - The Mechanobiology of Obesity and Related Diseases - page 37

Fig. 2 Effect of cyclic stretching on adipocyte differentiation of 3T3-L1 cells. a. Undifferen-
tiated 3T3-L1 cells at confluence. b. 3T3-L1 cells at the end of induction period with resting
condition (100 % length). c. Oil-Red-O-stained image of post-maturation-period cells with
resting condition (100 % length). d. 3T3-L1 cells with static stretching to 150 % in order to
secure mechanical responsiveness. e. 3T3-L1 cells with cyclic stretching (130 %, 1 Hz) during
the induction period of 2 days. f. Oil-Red-O-stained image of post-maturation-period cells with
resting condition (100 % length) that were subjected to cyclic stretching (130 %, 1 Hz) during
the induction period. Scale bar indicates 100 lm
that is caused by a downregulation of PPARc 2 transcript without any appreciable
changes in C/EBPs [ 14 ].
Significant morphological changes were observed even during the induction
period, when mitotic clonal expansion occurs [ 16 ]. It has been suggested that the
correct cytoskeletal rearrangements are prerequisite for terminal differentiation [ 2 ,
17 , 18 ]. Cyclic uniaxial stretching to two-dimensionally adherent cells, including
preadipocytes [ 14 , 15 ], fibroblasts [ 19 ], cardiac myocytes [ 20 ], vascular smooth
muscle cells [ 19 , 21 ] and endothelial cells [ 22 ], etc., induces elongation and ori-
entation perpendicular to the direction of the stretching irrespective of cell types
(Fig. 2 ). The cyclic stretch-induced cell orientation depends on Ca 2+ influx via
stretch-activated cation channels [ 22 ], tyrosine phosphorylation by c-Src in focal
adhesion complexes (pp130 CAS , pp125 FAK , paxillin) [ 23 ], activation of extracel-
lular signal-regulated protein kinase/mitogen-activated protein kinase (ERK/
MAPK) and p38/MAPK [ 24 ] and Rho-GTPase [ 25 ]. Interestingly, the stretch-
induced unidirectionally oriented response of the cells disappeared with the
administration of PD98,059, an inhibitor of ERK/MAPK-kinase (MEK), suggesting