The bone vasculature plays a vital role in bone homeostasis and remodeling. Reduced or inadequate blood flow has been linked to impaired fracture healing and old age-related osteoporosis. Endothelial adaptations are likely to be critical to vascular and skeletal changes that occur with disuse in old age, and may be remedied by exercise training. We have demonstrated that low-intensity, low-impact aerobic exercise training stimulates improved endothelial function in skeletal resistance arteries in old rats, however, the exercise training stimuli that drive adaptations of the aged skeletal microcirculation remain unknown. In this proposal we will identify skeletal microvascular adaptations that occur in response to either aerobic exercise training or targeted muscular stretch training. Bouts of aerobic locomotory exercise increase blood flow to muscle and long bones. In contrast, bouts of static stretching reduce muscle blood flow and increase bone strain without altering localized skeletal blood flow at the site of muscle attachment. Therefore, we will test the overall hypothesis that intervention-specific microvascular adaptations will be induced in aged long bones of rats that undergo low-intensity aerobic training as compared to rats that undergo muscular stretch training. Specifically, in Aim 1, we will determine whether a program of low-intensity low-impact aerobic exercise training produces homogeneous vasculogenesis and increases total perfusion of the long bones of old rats. We hypothesize that this aerobic locomotory exercise training will 1) increase bone and marrow blood flow at rest and during exercise in old rats, 2) induce vasculogenesis throughout the long bones of old rats, and 3) improve nitric oxide signaling by reducing oxidant stress and inflammation of the endothelium.
In Aim 2, we will determine whether a program of muscular stretch training produces localized vasculogenesis and increases localized perfusion of the long bones of old rats. We hypothesize that muscular stretch training will 1) increase localized (in the proximity of muscular attachment) blood flow at rest and during exercise in the long bones of old rats, 2) induce localized vasculogenesis (in the proximity of muscular attachment) within the long bone of old rats, and 3) improve endothelium-dependent, nitric oxide-mediated vasodilation of the proximal nutrient artery primarily through reduction of endothelial inflammation and oxidant stress. Identification of these training-specific adaptive mechanisms will provide novel insight into adaptations of the skeletal microvasculature that can be targeted therapeutically in clinical settings, including age-related osteoporosis and fracture healing, even if fracture results in immobility.
With age in humans, there is a decline in bone mass and bone blood flow that contributes to bone fragility and increased risk for fractures. Loading of the bones during exercise may increase bone mass and bone blood flow, even during old age; however, the signals that are created by exercise that stimulate bone blood flow and bone formation remain unclear. This proposal will investigate the means by which two distinct types of exercise, aerobic treadmill exercise versus static muscular stretching, stimulate formation of bone and blood vessel growth within bone.
