NFAT signaling: choreographing the social lives of cells.
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Calcium signaling activates the phosphatase calcineurin and induces movement of NFATc proteins into the nucleus, where they cooperate with other proteins to form complexes on DNA. Nuclear import is opposed by kinases such as GSK3, thereby rendering transcription continuously responsive to receptor occupancy. Disruptions of the genes involved in NFAT signaling are implicating this pathway as a regulator of developmental cell-cell interactions. (+info)
The effect of endurance exercise on the morphology of muscle attachment sites.
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The morphology of muscle attachment sites, or entheses, has long been assumed to directly reflect in vivo muscle activity. The purpose of this study is to examine whether variations in muscle activity that are within normal physiological limits are reflected in variations in external attachment site morphology. This study tests the hypothesis that increased muscle activity (magnitude, number and frequency of loading cycles) results in the hypertrophy of muscle attachment sites. The attachment sites of six limb muscles and one muscle of mastication (control) in mature female sheep were measured and compared in exercised (weighted treadmill running for 1 h per day for 90 days) and sedentary control animals. Attachment site surface morphology was assessed by quantifying the size (3D surface area) and complexity (fractal dimension parallel and perpendicular to soft tissue attachment) of the surfaces. The results of this study demonstrate no effect of the exercise treatment used in this experiment on any measure of enthesis morphology. Potential explanations for the lack of exercise response include the mature age of the animals, inappropriate stimulus type for inducing morphological change, or failure to surpass a hypothetical threshold of load for inducing morphological change. However, further tests also demonstrate no relationship between muscle size and either attachment site size or complexity in sedentary control animals. The results of this study indicate that the attachment site morphological parameters measured in this study do not reflect muscle size or activity. In spite of decades of assumption otherwise, there appears to be no direct causal relationship between muscle size or activity and attachment site morphology, and reconstructions of behavior based on these features should be viewed with caution. (+info)
Early effects of embryonic movement: 'a shot out of the dark'.
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It has long been appreciated that studying the embryonic chick in ovo provides a variety of advantages, including the potential to control the embryo's environment and its movement independently of maternal influences. This allowed early workers to identify movement as a pivotal factor in the development of the locomotor apparatus. With an increasing focus on the earliest detectable movements, we have exploited this system by developing novel models and schemes to examine the influence of defined periods of movement during musculoskeletal development. Utilizing drugs with known neuromuscular actions to provoke hyperactivity (4-aminopyridine, AP) and either rigid (decamethonium bromide, DMB) or flaccid (pancuronium bromide, PB) paralysis, we have examined the role of movement in joint, osteochondral and muscle development. Our initial studies focusing on the joint showed that AP-induced hyperactivity had little, if any, effect on the timing or scope of joint cavity elaboration, suggesting that endogenous activity levels provide sufficient stimulus, and additional mobilization is without effect. By contrast, imposition of either rigid or flaccid paralysis prior to cavity formation completely blocked this process and, with time, produced fusion of cartilaginous elements and formation of continuous single cartilaginous rods across locations where joints would ordinarily form. The effect of these distinct forms of paralysis differed, however, when treatment was initiated after formation of an overt cavity; rigid, but not flaccid, paralysis partly conserved precavitated joints. This observation suggests that 'static' loading derived from 'spastic' rigidity can act to preserve joint cavities. Another facet of these studies was the observation that DMB-induced rigid paralysis produces a uniform and specific pattern of limb deformity whereas PB generated a diverse range of fixed positional deformities. Both also reduced limb growth, with different developmental periods preferentially modifying specific osteochondral components. Changes in cartilage and bone growth induced by 3-day periods of flaccid immobilization, imposed at distinct developmental phases, provides support for a diminution in cartilage elaboration at an early phase and for a relatively delayed influence of movement on osteogenesis, invoking critical periods during which the developing skeleton becomes receptive to the impact of movement. Immobilization also exerts differential impact along the proximo-distal axis of the limb. Finally, our preliminary results support the possibility that embryonic hyperactivity influences the potential for postnatal muscle growth. (+info)
Mechanical influences on bone development in children.
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