Satellite cell and myonuclear distribution within normal and hypertrophic models of skeletal muscle growth, and the expression of myogenic regulatory factors during growth
Date
2007-05-31
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Type
Degree Level
Doctoral
Abstract
Satellite cells (SCs) are mononuclear myogenic stem cells located between the basal lamina and plasmalemma of the skeletal muscle fiber. They are responsible for postnatal skeletal muscle growth, repair and regeneration. Once activated, SCs divide and fuse to the muscle fibers where their nuclei become new myonuclei. Earlier studies suggested that SCs were either randomly or evenly distributed along muscle fibers. However, myonuclei were found to be more concentrated at tapered ends of muscle fibers. Myogenic regulatory factors, mainly MyoD and Myogenin, are expressed by active SCs. Previous in vitro and prenatal studies suggested that MyoD expression demarcates the end of proliferation while Myogenin can demarcate the differentiation stage within myoblasts. Few in vivo studies have reported the expression of MyoD and Myogenin within SCs, and none have attempted to discern their expression patterns during growth. Meat producing chickens represent a unique model for natural hypertrophy within muscle fibers. However, very little is known about the distribution of SCs within these naturally hypertrophied fibers, and whether this distribution is comparable to that of experimental models of hypertrophy. Nandrolone Decanoate is the anabolic steroid most commonly used to increase skeletal muscle mass and strength, although little is known of its effects on SCs. This thesis expands our understanding of SCs by examining the following hypotheses: 1) there is a greater frequency (number of SC nuclei over all nuclei within the basal laminae) and a higher concentration (less surface area of sarcolemma per SC) of SCs at the ends of developing skeletal muscle fibers, 2) MyoD and Myogenin transcription myogenic factors have distinctive patterns of expression within SC nuclei during maturation, 3) there are greater frequency and concentration of SCs and greater number of myonuclei in naturally hypertrophied muscle fibers compared to their control, and 4) there is a greater frequency and a greater concentration of SCs in Nandrolone treated birds than in controls. Chicken pectoralis muscle was the main experimental model used in this thesis because of its overlapping fibers arranged in series, the presence of neonatal myosin at the fiber ends and relative homogeneity of fiber type. Immunocytochemical techniques that include an antibody against Pax7 to identify SC nuclei were applied, and computer image analyses were then used to quantify the numbers of SC nuclei and myonuclei within muscle fibers. This thesis demonstrates that throughout development there is a greater frequency and concentration of SCs at the ends of developing skeletal muscle fibers, which indicates a major contribution of these cells in the longitudinal growth of muscle fibers. It also reveals that MyoD and Myogenin each has a distinctive pattern of expression within SCs during in vivo postnatal development. The expression of MyoD increases significantly during maturation, while Myogenin expression remains steady. This finding suggests that each of these myogenic factors play a different role in the postnatal activation of SCs. Lastly, it is the first study to show a greater frequency and a higher concentration of SCs within both naturally and Nandrolone induced hypertrophied muscle fibers. This indicates SCs may be critically involved during postnatal skeletal muscle growth and hypertrophy.
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Keywords
Nandrolone Decanoate, Myosin
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Anatomy and Cell Biology
Program
Anatomy and Cell Biology