Biomedical Engineering Reference
In-Depth Information
activating the MEK-ERK/MAPK signaling pathway [
36
,
38
]. The author sug-
gested that sustained static stretching delivered to differentiating adipocytes within
a certain physiological range could stimulate them to produce lipid, implying
certain physiological situations such as a sedentary lifestyle, which is connected to
an overweight condition and obesity [
10
,
36
,
38
]. On the contrary, the static
uniaxial stretching at 125 % length (of which the extending level may be a
physiatric level), which was applied throughout the whole differentiation period
(25 days), significantly inhibits 3T3-L1 adipogenesis as judged by microscopic
observation of intracellular lipid accumulation and other biochemical markers such
as cytoplasmic glycerol-3-phosphate dehydrogenase (GPDH) activities (Tanabe
et al., unpublished observation). Different results regarding the inhibitory or the
stimulatory regulation of adipogenesis by mechanical stretching might be due to
the different intensities of mechanical stimuli depending on the stretch-length and/
or signaling specificity to the different types of mechanical forces applied such as
uniaxial and multiaxial stretching [
106
].
3.6 Cyclooxygenase Pathway
It has been demonstrated that some cyclooxygenase products could affect adipo-
cyte differentiation both positively and/or negatively depending on the classes of
prostaglandins (PGs); for example, PGI
2
promotes adipocyte differentiation [
107
],
whereas PGF
2
a [
108
] and PGE
2
[
109
] each inhibits the differentiation. In this
regard, it was found that arachidonic acid (AA), an x-6 polyunsaturated fatty acid
(PUFA) and a precursor of PG synthesis, strongly inhibits adipocyte differentiation
via a pathway dependent on the PG synthesis [
110
]. The inhibitory effect of AA
was associated with sustained expression of cyclooxygenases (COX-1 and COX-2)
[
110
]. Furthermore, PGE
2
-EP4 receptor signaling suppresses adipocyte differen-
tiation by down-regulation of PPARc
2
expression in an autocrine manner [
111
]. It
has been reported that expression of COX-2 was transiently induced, whereas
expression of COX-1 was constant during induction of differentiation [
15
,
110
,
111
]. Therefore, intentional change in the COXs expression and/or their activity
may modulate adipocyte differentiation.
COX-2 has been implicated in the regulation of body fat, as mice heterozygous
for the COX-2 gene develop obesity [
112
]. Mechanical stresses, including cyclic
stretching, have been reported to augment COX-2 expression in several types of
cells [
15
,
39
,
113
-
118
]. The molecular mechanism as to the stretch-induced COX-
2 expression seems to be somewhat varied depending on the cell types and/or
stretching protocols. In the case of human fibroblast by cyclic uniaxial stretching,
for example, increase in the intracellular Ca
2+
concentration via stretch-activating
channel initially occurred, then the following events proceeded sequentially, i.e.,
production of reactive oxygen species (ROS), activation of inhibitor of nuclear
factor jB(IjB)—kinase (IKK), phosphorylation of IjB, and nuclear translocation
of nuclear factor jB(NF-jB) [
113
]. Involvement of activator protein-1 (AP-1),
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