Biomedical Engineering Reference
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another transcription factor formed by dimerization of c-Fos and c-Jun, in the
static stretch-induced COX-2 expression has been also reported; where AP-1, but
not NF-jB, was involved in the static stretch-induced COX-2 expression by pri-
mary human uterine myocytes [
118
], and both AP-1 and NF-jB contributed in the
case of human primary amniotic cells [
119
]. Either AP-1 or NF-jB (or both)
would activate COX-2 gene expression through binding the promoter region [
120
].
Alternatively, in the case of fetal lung epithelial cells [
114
], the cyclic stretching
triggered an increase in Ca
2+
influx and activation of ERK/MAPK, both of which
are conjointly required for full activation of cytosolic phospholipase A
2
(cPLA
2
)
[
121
], and would lead to an efficient AA release and subsequent COX pathway
increases triggering synthesis of various PGs [
114
]. Furthermore, production of
PGF
2
a in differentiating 3T3-L1 cells forms a positive feedback loop that coor-
dinately suppresses the early stage of adipogenesis through the increased pro-
duction of PGF
2
a and PGE
2
, i.e., PGF
2
a—FP receptor—ERK/MAPK activation—
cyclic AMP responsive element binding protein (CREB)—COX-2 gene expres-
sion—PGF
2
a and PGE
2
[
98
]. Collectively, mechanical control of COX-2
expression may explain a part of the inhibitory effect of stretching on 3T3-L1
adipogenesis via augmented production of these inhibitory PGs (Fig.
3
). Further
experiments will be necessary to clarify the mechanism in more detail.
3.7 Wnt Signal
The Wnt family consists of several members of secreted glycoproteins having key
roles of differentiation and cell fate through cell surface receptor mediated para-
and/or autocrine mechanisms. Wnt signaling is known to play a significant role
in specifying differentiating cell fates of mesenchymal stem cells such as
osteoblast-to-adipoblast [
122
-
124
], myoblast-to-adipoblast [
125
] and chondro-
blast-to-osteoblast [
126
,
127
] switches.
As to the relationship with adipogenic differentiation [
3
,
4
], the Wnt10B/b-
catenin signal, which is known as canonical Wnt signaling, has been shown to
express constitutively in preadipocytes but not mature adipocytes and could inhibit
adipocyte differentiation by blocking the expression of PPARc and C/EBPa
[
4
,
128
]. On the contrary, Wnt5B, a non-canonical Wnt ligand, is transiently
induced during adipogenesis and promotes adipogenesis by preventing the
canonical Wnt/b-catenin pathway [
129
]. Wnt5A, a paralog of Wnt5B, has been
shown to possess opposite roles in adipogenesis, i.e., Wnt5A promotes adipo-
genesis in committed preadipocytes 3T3-L1 [
130
,
131
], whereas the Wnt5A sig-
naling inactivates the PPARc function through a chromatin inactivation, leading to
an osteoblastic cell lineage from mesenchymal stem cells [
132
]. Interestingly, it
was reported that the cyclic stretching to 120 % of the original length with a
frequency of 0.1 Hz, inhibited the cocktail-stimulated adipogenesis of C2C12
myoblasts via increased expression of Wnt10B (Fig.
3
); this inhibitory effect was
attenuated by a soluble Wnt ligand sFRP-2 [
26
]. Furthermore, the cyclic biaxial
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