Research opportunities in muscle atrophy

Muscle atrophy in a weightless environment is studied. Topics of investigation include physiological factors of muscle atrophy in space flight, biochemistry, countermeasures, modelling of atrophied muscle tissue, and various methods of measurement of muscle strength and endurance. A review of the current literature and suggestions for future research are included

Research opportunities in muscle atrophy

A trophy of skeletal muscle; muscle a trophy associated with manned space flight; the nature, causes, and mechanisms of muscle atrophy associated with space flight, selected physiological factors, biochemical aspects, and countermeasures are addressed

Translational Models for Advancement of Regenerative Medicine and Tissue Engineering

At the root of each regenerative medicine or tissue engineering breakthrough is a simple goal, to improve quality of healing, thus improving a patient’s quality of life. Each tissue presents its own complexities and limitations to healing, whether it is the scarring nature of tendon healing or the mechanical complexity driving bone regeneration. Preclinical, translational models aim to reflect these complexities and limitations, allowing for effective development and refinement of tissue engineered therapeutics for human use. The following body of work explores several of these translational models, both utilizing them for tissue regenerative therapy development and evaluating the benefits and complications incurred with each model. This work begins with a discussion of the complexity of bone healing and how dysfunction in the mechanical, surgical, and systemic fracture environment can lead to delayed healing and nonunion. A comprehensive review of the advances in preventative and corrective therapeutics for bone nonunion is included next, with specific focuses on mechanical and tissue-engineered technology. Then, this work presents a tissue-engineered application of mesenchymal stem cells in acute tendon injury, highlighting experimentation in cell fate direction in vitro and intralesional mesenchymal stem cell implantation in vivo. Next, this work presents a series of experiments that evaluated and refined a commonly utilized preclinical model of delayed bone healing, the caprine segmental tibial defect stabilized using single locking plate fixation. First, the biomechanical stability of the model was evaluated in vivo using plantar-pressure analysis of gait. Then, the surgical technique was refined through a retrospective analysis of the effects of plate length and position on fixation stability in vitro and in vivo. Finally, the comorbidities of this preclinical model were explored via an analysis of the effect of long-term tibial locking plate fixation on cortical dimensions and density

Progression of microstructural deterioration in load-bearing immobilization osteopenia

PurposeImmobilization osteopenia is a major healthcare problem in clinical and social medicine. However, the mechanisms underlying this bone pathology caused by immobilization under load-bearing conditions are not yet fully understood. This study aimed to evaluate sequential changes to the three-dimensional microstructure of bone in load-bearing immobilization osteopenia using a fixed-limb rat model.Materials and methodEight-week-old specific-pathogen-free male Wistar rats were divided into an immobilized group and a control group (n = 60 each). Hind limbs in the immobilized group were fixed using orthopedic casts with fixation periods of 1, 2, 4, 8, and 12 weeks. Feeding and weight-bearing were freely permitted. Length of the right femur was measured after each fixation period and bone microstructure was analyzed by micro-computed tomography. The architectural parameters of cortical and cancellous bone were analyzed statistically.ResultsFemoral length was significantly shorter in the immobilized group than in the control group after 2 weeks. Total area and marrow area were significantly lower in the immobilized group than in the control group from 1 to 12 weeks. Cortical bone area, cortical thickness, and polar moment of inertia decreased significantly after 2 weeks. Some cancellous bone parameters showed osteoporotic changes at 2 weeks after immobilization and the gap with the control group widened as the fixation period extended (P < 0.05).ConclusionThe present results indicate that load-bearing immobilization triggers early deterioration of microstructure in both cortical and cancellous bone after 2 weeks

Influence of Castration and and a High Protein Diet on Load-Mediated Hypertrophy and Skeletal Muscle Force Production in Rats Following Immobilization

The purpose of the present study to was to to examine the effects of low testosterone on muscle mass and function in rats following 10 days of hindlimb immobilization and determine if a high protein diet enhances load-mediated hypertrophy. Average SOL CSA was significantly lower for immobilized vs. control legs at 0 (30.3%, p < 0.001) and 14 days of reloading (15.9%, p = 0.006). Significant differences in average soleus mass were present at all days of reloading (all p < 0.001). Immobilized SOL Po followed a similar pattern (all p < 0.001), and castrated animals showed lower Po at 14 days (p < 0.050). At present, functional overload in a testosterone-deprived state appears to reduce the regrowth of skeletal muscle size, suggesting that testosterone may play a role in load-mediated hypertrophy following immobilization. As well, a high protein diet did not result in enhanced load-mediated hypertrophy in castrated rats.Master of Art

Biomedical Research Division significant accomplishments for FY 1983

Various research and technology activities of Ames Research Center's Biomedical Research Division are described. Contributions to the Space Administration's goals in the life sciences include research in operational medicine, cardiovascular deconditioning, motion sickness, bone alterations, muscle atrophy, fluid and electrolyte changes, radiation effects and protection, human behavior and performance, general biomedical research, and gravitational biology

In Vitro Simulation of Microgravity Induced Muscle Loss Successfully Increases Expression of Key In Vivo Atrophy Markers

Muscle loss from lack of activity is a serious issue for immobilized patients on Earth and in human spaceflight, where the low gravity environment prevents normal muscle activity. Simulating muscle loss in cultured cells is an important step in understanding how this condition occurs. This work evaluates different means of simulating muscle loss and selects the one that most closely mimics the cellular responses seen in animals and humans. To simulate the microgravity environment of spaceflight, mouse skeletal muscle cells were grown in a rotary cell culture system (RCCS). Growing the cells within a natural gelled substrate was compared against growing them on the surface of small plastic beads. Changes after culture under simulated microgravity were characterized by assessing proteins and genes known to change during muscle loss. The structure of the cells was also evaluated by microscopy. The mouse skeletal muscle cells grown on plastic beads in the RCCS had significant changes in multiple key genes associated with muscle loss and demonstrated physical characteristics expected of mature tissue in live animals. This model is a valuable platform for exploring muscle loss mechanisms and testing new drugs

Prevention of muscle wasting and osteoporosis: the value of examining novel animal models

Bone mass and skeletal muscle mass are controlled by factors such as genetics, diet and nutrition, growth factors and mechanical stimuli. Whereas increased mechanical loading of the musculoskeletal system stimulates an increase in the mass and strength of skeletal muscle and bone, reduced mechanical loading and disuse rapidly promote a decrease in musculoskeletal mass, strength and ultimately performance (i.e. muscle atrophy and osteoporosis). In stark contrast to artificially immobilised laboratory mammals, animals that experience natural, prolonged bouts of disuse and reduced mechanical loading, such as hibernating mammals and aestivating frogs, consistently exhibit limited or no change in musculoskeletal performance. What factors modulate skeletal muscle and bone mass, and what physiological and molecular mechanisms protect against losses of muscle and bone during dormancy and following arousal Understanding the events that occur in different organisms that undergo natural periods of prolonged disuse and suffer negligible musculoskeletal deterioration could not only reveal novel regulatory factors but also might lead to new therapeutic options. Here, we review recent work from a diverse array of species that has revealed novel information regarding physiological and molecular mechanisms that dormant animals may use to conserve musculoskeletal mass despite prolonged inactivity. By highlighting some of the differences and similarities in musculoskeletal biology between vertebrates that experience disparate modes of dormancy, it is hoped that this Review will stimulate new insights and ideas for future studies regarding the regulation of atrophy and osteoporosis in both natural and clinical models of muscle and bone disuse

NASA Workshop on Biological Adaptation

A workshop was convened to review the current program in Space Biology Biological Adaptation Research and its objectives and to identify future research directions. Two research areas emerged from these deliberations: gravitational effects on structures and biomineralization and gravity affected regulatory mechanisms. The participants also recommended that research concentrate on rapidly growing animals, since gravity effects may be more pronounced during growth and development. Both research areas were defined and future research directions were identified. The recommendations of the workshop will assist the Life Sciences Division of NASA in it assessment and long-range planning of these areas of space biology. Equally important, the workshop was intended to stimulate thought and research among those attending so that they would, in turn, interest, excite, and involve other members of the academic community in research efforts relevant to these programs