Mechanical Stretching and Signaling Pathways in Adipogenesis - The Mechanobiology of Obesity and Related Diseases - page 38

a link between this orienting response and the inhibition of adipocyte differentiation
through the activation of the ERK/MAPK pathway [ 14 ].
Several groups have demonstrated that the effects of mechanical stimuli,
including cyclic stretching [ 14 , 15 , 26 - 34 ], static stretching [ 35 - 38 ], and com-
pressive force [ 39 - 41 ] on several differentiation models using mouse [ 14 , 15 , 38 ]
or human preadipocytes [ 39 ], and mesenchymal stem cells (MSCs) from mouse
[ 26 , 29 , 30 , 32 , 40 , 41 ], rat [ 31 , 34 ], human [ 28 , 33 ], and bovine [ 27 ], respectively.
While these mechanical stimulations tend to inhibit adipogenesis of preadipocytes
and MSCs by downregulation of PPARc via several mechanotransduction path-
ways (see following sections) [ 26 - 30 , 33 , 34 , 39 - 41 ], it has been also reported that
accelerated lipid production of differentiating 3T3-L1 cells by the static and
prolonged stretching within a physiological range, the production of which is
mostly independent of PPARc activation [ 36 - 38 ]. These results suggest that the
mechanical stimulus may differentially affect adipogenesis in either a stimulatory
or inhibitory manner presumably depending on the strength and/or duration or
timing of mechanical input as well as cellular differentiation statuses. Proposed
mechanisms will be discussed in the following sections.
3 Mechanotransduction that Affects Adipogenesis
3.1 Mechanosensing Molecules
Generally, mechanosensitive cells show highly reproducible responses to each
kind of mechanical stimulation. However, the mechanical factors are essentially
non-selective in nature; thus it is difficult to assume that there are any specific
mechanosensing mechanisms in each cell type. Nevertheless, a variety of me-
chanosensing molecules, thought to transduce mechanical forces into intracellular
signals, have been proposed [ 42 ]: e.g., mechanically gated ion channels [ 43 - 46 ],
membrane-integrated growth factor receptors [ 47 ], G-protein coupled receptors
[ 48 ], integrins and other cell-adhesion molecules [ 49 ], Rho-GTPase family [ 19 ]
and force-triggered G-actin release and F-actin remodeling by formins [ 50 ], etc.
Although no specific mechanosensory mechanism concerning mechanotransduc-
tion in mesenchymal/mesodermal lineage including adipocytes has been proposed,
significant progress has been made in this field as follows.
3.2 Cellular Mechanical Properties and Cytoskeletal
Controls
The stromal-vascular fraction of white adipose tissue contains multipotent mes-
enchymal stem cells (MSCs), known as adipose-derived stem cells (ASCs) [ 51 ].