Biomedical Engineering Reference
In-Depth Information
2.5.6 Mechanisms for bone adaptation to
mechanical loading
The mechanosensitivity of the skeleton has long been established; however, the
precise mechanisms underlying this response remain uncertain. It is logical to
assume that the process involves some form of mechanotransduction, which
refers to the conversion of a biophysical force into a cellular response.
193
It
is a generic process whose role is to enable living organisms to respond to
their mechanical environment. a model for mechanotransduction in bone is
illustrated in Fig. 2.13.
Osteoblasts, bone-lining cells and osteocytes have all been shown to
respond to mechanical stimulation; however, it is the osteocyte that appears
anatomically to be the best positioned to sense and convey changes in the
local mechanical environment.
96
This results from the sheer numbers and
distribution of osteocytes throughout the bone matrix and their high degree
of interconnectivity.
94
Recent evidence investigating the role of an osteocyte-
specific protein (sclerostin, the protein product of the SOST gene) supports
osteocytes as the primary mechanosensory cell, to the exclusion of the other
bone cell types (i.e. osteoblasts and bone lining cells).
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even though osteocytes are thought to be mechanosensors, there is little
conclusive data to show how mechanical loading is sensed by these cells.
One of the more accepted forms is the flow of bone interstitial fluid driven by
extravascular pressure in combination with applied mechanical loading.
194, 195
This theory has support from studies demonstrating mechanically enhanced
transport within the lacunar-canalicular system of bone.
95
Fluid flow along
cell bodies or processes produces drag force, fluid shear stress and an
electrical potential called a streaming or stress-generated potential. each
of these signals may activate bone cells, although cell culture experiments
suggest that cells are more sensitive to fluid forces than they are to electrical
potential.
195, 196
Fluid shear stresses on osteocytes appear to deform the cells
within their lacunae and the cellular dendrites within the canaliculi.
195
It
may also influence the primary cilium that projects extracellularly from the
osteocyte cell body.
197
Following detection of a local mechanical stimulus, the signal needs to be
translated into a cellular response by the sensor. Mechanical deformation of
a cell membrane by fluid shear stresses may have a direct influence on the
cellular translation of mechanical stimuli.
198, 199
The phospholipid membrane
of bone cells contains membrane spanning glycoproteins called integrins.
extracellularly, these integrins connect with the collagen of the organic matrix
via specific receptors for extracellular matrix proteins.
199, 200
Intracellularly, they
attach to the intracellular cytoskeleton which, in turn, connects to the nuclear
membrane and other cytoplasmic constituents.
201
The result is the formation
of a continuous network called the extracellular matrix-integrin-cytoskeleton
