Biomedical Engineering Reference
In-Depth Information
by Donahue et al. [
24
]. They observed a modest, but statistically significant,
reduction in the frequency of Ca
2+
i
oscillations under both static and fluid flow
conditions in osteoblasts derived from old rats (24 mos.) versus osteoblasts derived
from mature rats (12 mos.); interestingly, there was no difference in the magnitude
of the response across the age groups, similar to the study of Kamioka et al.
Increases in Ca
2+
i
signaling are linked to the expression of markers implicated
in bone modeling and remodeling, such as insulin-like growth factor (IGF)
[
47
,
61
], nitric oxide (NO) [
42
,
59
,
79
], prostaglandins [
42
,
47
,
79
], TGF-b
1
[
88
],
and ATP [
30
]. While Donahue et al. remains the only study to examine whether
the Ca
2+
i
response to fluid shear stress is affected by donor age, a larger number of
studies have reported whether the release of such paracrine and autocrine factors as
NO, IGF, and prostaglandins, is affected by osteoporosis.
Sterck et al. [
94
] examined whether osteoblastic cells derived from trabecular
bone biopsies normal (mean age 67 y) or osteoporotic donors (mean age 61 y)
were similarly affected by mechanical stress. Cells from both donor groups
demonstrated an increase in alkaline phosphatase activity and osteocalcin release
in response to 10 nM 1a, 25-dihydroxyvitamin D
3
, indicating that both cell sources
were osteoblastic in phenotype. In response to a pulsatile shear stress of
0.7 ± 0.03 Pa applied at a frequency of 5 Hz, osteoblastic cells from both non-
osteoporotic and osteoporotic donors significantly increased the release of pros-
taglandin E
2
(PGE
2
) and NO after 1 h. A difference between non-osteoporotic and
osteoporotic donor cell responsiveness was only found 24 h after cessation of fluid
shear stress, at which point cells from non-osteoporotic donors continued to release
PGE
2
, whereas cells from osteoporotic donors did not. Since PGE
2
and NO release
are influenced by fluid shear stress-induced Ca
2+
i
oscillations, these data suggest
that the modest decrease in the percent of aged osteoblastic cells to respond to fluid
flow, as observed by Donahue et al. [
24
], may not affect the ability of an osteo-
blastic cell to generate of soluble mediators like NO or PGE
2
.
In a related study, Bakker et al. examined the influence of pulsatile fluid shear
stress upon NO and PGE
2
release in primary bone cells cultured from osteoporotic
(OP) or osteoarthritic (OA) donors [
5
]. Osteoblastic cells from both OA and OP
donors responded to a pulsatile shear stress of 0.6 ± 0.3 Pa (5 Hz) by increasing
release of NO and PGE
2
; increased PGE
2
release was paralleled with increased
transcription of COX-2, the inducible enzyme responsible for PG synthesis. This
would indicate that osteoblastic bone cells from aged (mean age 78 y for OP, 75 y
for OA), diseased individuals are still capable of responding to an in vitro
mechanical stimulus, suggesting that the capacity of cells to respond is unaffected
by aging or disease state. They also examined whether mechanosensitivity was
different in OA versus OP cultures, by examining the NO and PGE
2
response at
varying shear rates. Varying the magnitude of applied shear stress revealed dif-
ferences in mechanoresponsiveness between the OA and OP groups. Both PGE
2
and NO release were greater in OP-derived than OA-derived osteoblasts at lower
shear stress (0.4 ± 0.1 Pa). However, since there was no comparison to osteo-
blastic cells from asymptomatic elderly patients, one cannot conclude whether this
differential mechanosensitivity is due to disease. The same group did examine the
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