Biomedical Engineering Reference
In-Depth Information
Once released, aTP binds with purinergic (P2) receptors, which can be
divided into two families—metabotropic G protein-linked P2Y receptors and
ionotropic P2X receptors.
212
activation of these receptors results in an increase
in intracellular ca
2+
.
213, 214
P2Y receptor activation increases intracellular
ca
2+
levels by stimulating the release of ca
2+
from intracellular stores via a
phospholipase c (PLc)-phosphatidylinositol bisphosphate (PIP
2
)-inositol
triphosphate (IP
3
) pathway, whereas P2X receptors are ligand-gated ion
channels which form pores within the cell membrane allowing permeation
of extracellular ca
2+
.
112
activation of the P2 receptors, and in particular the P2X
7
receptor, influences
the adaptive response of bone to mechanical loading. In particular, as much
as 73% of the osteogenic response to loading
in vivo
has been linked to the
P2X
7
receptor.
215
The downstream mechanism/s by which P2 activation and the
increase in intracellular ca
2+
results in signal transmission required for bone
adaptation is not yet resolved. however, it has been shown that P2 signaling
modulates cyclooxygenase-2 (cOX-2) expression
216
and prostaglandin
release.
217, 218
cOX-2 is the rate limiting enzyme in the conversion of
arachidonic acid to prostaglandins. Prostaglandins have effects on bone
formation and resorption, which are mediated through the proliferation and
differentiation of osteoblasts and the regulation of osteoclast differentiation.
219
The upregulation of cOX-2 and subsequent release of prostaglandins following
mechanical loading is important in regulating an effector response, as
inhibition of cOX-2 reduces the prostaglandin response
220, 221
and suppresses
mechanically induced bone adaptation.
222, 223
The signal is transmitted to the bone surface where it stimulates the
differentiation of precursor cells into osteoblasts to elicit a response. The
timing of a response following mechanical loading is similar among different
models of mechanical loading. studies in avian ulna compact bone have
shown that a single loading exposure transformed the periosteal cellular layer
from a quiescent to an osteogenic cell layer within five to seven days.
224, 225
In the rat tibia, mineral apposition rate was highest over a similar period,
five to eight days after a single loading bout.
226, 227
This increased bone
formation is believed to result from the activation of discrete packets of
osteoprogenitor cells which differentiate and synthesize osteoid.
227
Two days
following a single loading bout, osteoblast surface length increases with a
peak on day 3.
228
From days 5-12, bone formation rate is increased largely
owing to increases in bone forming surface.
227
nine days after a single
loading session, osteoblast surface length returns to normal.
2.6 Conclusions
In this chapter we presented details of the structure and function of bone
tissue in a hierarchical format, starting at the gross macroscopic level and
