Biomedical Engineering Reference
In-Depth Information
expression in bone and its role in repressing bone formation from the extra-
cellular space, SOST is an attractive target for anabolic therapeutics [34].
These facts make Wnt a suitable target to derive a bone anabolic response
[35]. On another note, Wnt pathway components, including Wnts, Fzds,
Lrps, and Tcf family members, are also expressed in osteoclast lineage cells
[36]. Thus, Wnts/β-catenin signaling appears to reduce bone resorption. It
remains for further investigation to resolve fully the scope of Wnt influences
on bone metabolism.
7.2.2 Mechanotransduction in Bone
The great majority of the cells of bone tissue, some 95% in the adult skeleton,
are osteocytes lying within the bone matrix and bone lining cells lying on
the bone surface [37]. Both osteocytes and bone lining cells are terminally
differentiated osteoblasts and have long been considered metabolically inac-
tive, with limited roles in bone biology. However, osteocytes remain in con-
tact with the bone surface cells and with neighboring osteocytes via long,
slender cell processes that are connected by means of gap junctions [38,39].
Their abundance and connectivity thus make them a three-dimensional net-
work for sensing mechanical strains.
The work reported in Nijweide, Burger, and Klein-Nulend [40] indicated
that osteocytes are the professional mechanosensory cells of bone and
lacuno-canalicular porosity is the structure that mediates mechanosensing.
It has also become clear that dynamic mechanical load causes fluid flow in the
lacuno-canalicular network [41]. Experiments in vivo [42] have indicated that
this fluid flow serves as the physical mediator of the mechanotransduction of
osteocytes and it is the fluid flow shear stress [43] that stimulates osteocytes
within minutes to produce signaling molecules [44] such as prostaglandins
(especially PGE
2
) [45] and NO [46], which modulate the activities of osteo-
blasts and osteoclasts, thus completing the transduction from mechanical
stimuli to biochemical signals [47]. NO is a strong inhibitor of bone resorp-
tion and acts by inhibiting RANKL expression in osteoblast precursors
while increasing OPG production in active osteoblasts, thus decreasing the
RANKL-OPG equilibrium and leading to reduced recruitment of osteoclasts
and positive bone formation [48]. Alternatively, PGE
2
has strong osteogenic
effects that contribute to increases in osteoblast differentiation from marrow
stromal cells through the EP
4
receptor [49].
7.2.3 Mathematical Model
The schematic diagram of the mathematical model structure of bone remod-
eling caused by mechanical loading is shown in Figure 7.2.
In biochemistry, the Hill equation is used to describe the fraction of the
macromolecule saturated by a ligand as a function of the ligand concentra-
tion; it is used in determining the degree of cooperativeness of the ligand
