Browsing by Subject "unloading"
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Item Mechanisms of impaired osteoblast function during disuse(Texas A&M University, 2004-11-15) Allen, Matthew RobertProlonged periods of non-weightbearing activity result in a significant loss of bone mass which increases the risk of fracture with the initiation of mechanical loading. The loss of bone mass is partially driven by declines in bone formation yet the mechanisms responsible for this decline are unclear. To investigate the limitations of osteoblasts during disuse, marrow ablation was superimposed on hindlimb unloaded mice. Marrow ablation is a useful model to study osteoblast functionality as new cancellous bone is rapidly formed throughout the marrow of a long bone while hindlimb unloading is the most common method used to produce skeletal unloading. The specific hypotheses of this study were aimed at determining if changes in osteoblast functionality, differentiation, and/or proliferation were compromised in non-weightbearing bone in response to a bone formation stimulus. Additionally, the influence of having compromised osteoblast functionality at the time of stimulation was assessed in non-weightbearing bones. Key outcome measures used to address these hypotheses included static and dynamic cancellous bone histomorphometry, bone densitometry, and real-time polymerase chain reaction (PCR) analyses of gene expression. The results document similar ablation-induced increases of cancellous bone in both weightbearing and unloaded animals. Similarly, there was no influence of load on ablation-induced increases in cancellous bone forming surface or mineral apposition rate. Unloading did significantly attenuate the ablation-induced increase in bone formation rate, due to reduced levels of total surface mineralization. When osteoblast functionality was compromised prior to marrow ablation, bone formation rate increases were also attenuated in ablated animals due to reduced mineralization. Additionally, increases in forming surface were attenuated as compared to unloaded animals having normal osteoblast function at the time of ablation. Collectively, these data identify mineralization as the limiting step in new bone formation during periods of disuse. The caveat, however, is that when bone formation is stimulated after a period of unloading sufficient to compromise osteoblast functionality, increases in osteoblast recruitment to the bone surface are compromised.Item Mitigating Disuse Bone Loss: Role of Resistance Exercise and Beta-Adrenergic Signaling(2011-08-08) Swift, Joshua MichaelMechanical loading is an integral component to maintaining bone mass during periods of disuse (i.e. bedrest or casting) or reduced weightbearing activity. Recent data has shown a direct relation between the sympathetic nervous system (SNS) and bone metabolism, however the underlying mechanisms responsible for this relationship are unknown. Furthermore, the role that beta adrenergic stimulation during disuse has on cancellous bone mass and microarchitecture have yet to be defined. The central hypothesis of this research is that resistance exercise and beta-1 adrenergic (Adrb1) receptor agonist administration attenuate disuse-associated reductions in metaphyseal bone during 28 days of rodent hindlimb unloading (HU). Study one determined whether an eccentric- (ECC) or combined isometric+eccentric- (ISO+ECC) based contraction paradigm, engaged during hindlimb unloading (HU), mitigates losses in musculoskeletal mass and strength. Both simulated resistance training (SRT) protocols inhibited reductions in disuse-sensitive cancellous bone mass and maintained plantarflexor muscle strength. Study two determined whether combining the anabolic effects of SRT with the anti-resorptive effects of alendronate (ALEN) during HU positively impacts cancellous bone in an additive or synergistic fashion. ALEN significantly inhibited the anabolic response of cancellous bone to SRT during HU. Study three determined whether an Adrb1 receptor agonist (dobutamine; DOB) mitigates disuse-associated losses in bone mass and formation rate (BFR) during HU. DOB administration significantly blunted reductions in bone mineral density (vBMD) by maintaining cancellous BFR. Study four determined if Adrb1 receptor agonist administration during HU results in an attenuation of osteocyte apoptosis within cancellous bone and whether this relates to a decrease in Bax/Bcl-2 mRNA content ratio (pro- and anti-apoptotic proteins). HU significantly increased cancellous bone osteocyte apoptosis and Bax/Bcl-2 mRNA content ratio, which was reduced by the administration of DOB. Collectively, these are the first studies to assess the role of beta-1 adrenergic signaling and resistance exercise in mitigating disuse-induced loss of cancellous bone mass in rodents. The long term goals of this research are to understand the exact molecular mechanisms by which both Adrb1 signaling and high intensity resistance exercise provide beneficial bone effects during prolonged periods of disuse and to apply these findings to current osteoporosis research.Item The role of load-regulating mechanisms In gaze stabilization during locomotion(2007-02-21) Tara Melaine Ruttley; Jacob Bloomberg; Ronita Cromwell; Golda A Kevetter-Leonard; Galen Kaufman; Ajitkumar MulavaraThe whole body acts as a gaze stabilization system: head-torso activity and lower body movement are coordinated to provide a stable retinal image during locomotion. Body loading is a fundamental parameter that modulates motor output during locomotion, and is especially important for controlling the generation of stepping patterns, dynamic balance, and termination of locomotion. Increased body weight support (BWS) during locomotion results in an immediate reorganization of locomotor control, such as a reduction in stance and double support duration and decreased hip, ankle, and knee angles during the gait cycle. Until now, no studies have investigated how gaze control systems respond to adaptive modification in the body load sensing system. The goal of this research is to determine the role of body load-regulating mechanisms in gaze control during locomotion. The general hypothesis behind the proposed research is that body load-regulating mechanisms contribute to gaze stabilization, and adaptive changes in these load-regulating mechanisms will require reorganization in the full-body gaze control system so that visual acuity can be maintained during locomotion. \r\nTo support the hypothesis of this study, head-torso coordination, lower limb movement patterns, and gait cycle timing were evaluated before and after a 30-minute adaptation session during which subjects walked on a treadmill at 5.4 km/hr with 40% body weight support (BWS). Before and after the adaptation period, head-torso and lower limb 3D kinematic data were obtained during locomotion using a video-based motion analysis system, and gait cycle timing parameters were collected by foot switches positioned under the heel and toe of the subjects’ shoes. The predominant changes observed in the subjects were a result of adaptive modification in the body load-regulating mechanisms and included increased head movements, increased knee and ankle flexion, and increased stance, stride, and double support time, with no change in dynamic visual acuity. Therefore, it is evident that just 30 minutes of 40% BWS during locomotion was enough sensory conflict to induce adaptive modifications in the sensory systems that contribute to locomotor control, and these modifications represent an overall reorganization of vestibular-somatosensory interactions in the full-body integrated gaze stabilization system. \r\n