Biomedical Engineering Reference
In-Depth Information
left-right patterning of the primary visceral organs is caused by ciliary left-ward
fluid flow in Hensen's node [ 18 , 39 ]. In the adult, resistance exercise promotes
skeletal muscle hypertrophy to functionally adapt to increases in applied loads
[ 33 ]. Just as mechanical forces promote functional adaptations to a changing
environment, perturbations in sensing and responding to mechanical forces play a
role in such diseases as cancer, atherosclerosis, asthma, and osteoporosis. Muta-
tions in dynein, a motor protein associated with cilia, can prevent left-ward fluid
flow in Hensen's node during embryogenesis; this causes the left-right patterning
of the internal organs to be random (heterotaxy) or reversed (situs inversus)
[ 39 , 53 , 93 , 95 ]. Within the cardiovascular system, laminar hemodynamic forces in
the heart are thought to be anti-atherogenic, whereas disturbed, turbulent flow is
thought to promote vascular remodeling and atherogenesis [ 9 , 73 , 89 , 109 ]. In the
absence of sufficient load, skeletal muscle undergoes atrophy.
The mammalian skeleton demonstrates tremendous capacity for functional
adaptation to mechanical forces. For example, conditions of reduced skeletal stress
promote bone resorption to minimize unnecessary energy expenditures, while
increased skeletal stress promotes bone formation that increases bone mass and
thereby reduces stress and/or strain upon subsequent loading. At the tissue and
cellular level, external mechanical forces promote changes in skeletal architecture by
altering proliferation and self-renewal, differentiation, matrix production and min-
eralization. Interestingly, the anabolic effect of physical activity promotes larger
changes in bone mass and strength in the young compared to the elderly [ 6 , 41 ].
A variety of factors—decreased muscle mass to generate load on bone [ 29 ], dimin-
ished sensitivity to mechanical stimuli with increased age [ 84 , 99 , 100 ], decreased
osteocyte number with age [ 26 , 62 ], or diminished capacity for matrix formation
[ 69 , 98 , 104 ]—may be altered, however, the relative roles of each are unknown.
Interestingly, there are conflicting reports as to the effects that aging has upon me-
chanoresponsiveness in vivo—for example, Rubin et al. showed that loading of
isolated turkey ulnae produced periosteal bone formation that was attenuated in older
animals [ 84 , 100 ] demonstrated a change in the threshold of mechanical strain
required for bone formation in young (9 month) versus old (19 month) rats. In con-
trast, Brodt and Silva recently demonstrated no loss of responsiveness to tibial
compression in aged mice compared to young adults [ 13 ]. Furthermore, exercise
studies in rodents show either reduced responsiveness with age [ 92 , 35 ], no influence
of age [ 40 , 77 , 102 ], and even enhanced responsiveness with age [ 15 , 54 ]. Despite the
appreciation of the socioeconomic burden of osteoporosis, the field of age-related
changes in mechanotransduction remains surprisingly fallow.
2 Mechanotransduction in Bone Cells
Mechanotransduction refers to the series of inter-related processes wherein
mechanical loading of the skeleton produces an adaptive response. All cells and
organisms are responsive to mechanical forces [ 38 , 39 , 68 ] however, with the
Search WWH ::




Custom Search