One consequence of surgical repair for ligament reconstruction or joint replacement is mechanical unloading/immobilization that results in muscle atrophy, compromising the ability of skeletal muscles to act as dynamic joint stabilizers. The sad truth is that very little is known about the mechanisms mediating the recovery of muscle mass and function following mechanical unloading/immobilization. The primary objective of this proposal then is to address the following issue: What mechanisms regulate the recovery of muscle mass and function following mechanical unloading/immobilization and how are these modulated by resistance training? In addressing this issue, a series of experiments is proposed centered around testing three fundamental hypotheses: i) the satellite cell hypothesis; ii) the transcription control hypothesis; and iii) the IGF-1 hypothesis. The satellite cell hypothesis states that recovery of muscle mass following mechanical unloading can only occur by activating satellite cells and increasing the pool of myonuclei. In contrast, the transcriptional control hypothesis postulates that the recovery on muscle mass and function can occur independent of satellite cell activation by upregulating the transcriptional activity of preexisting myonuclei. The IGF-1 hypothesis postulates that the reloading of skeletal muscle during the recovery process will initiate an autocrine/paracrine response involving IGF-1, and that this will, in turn, mediate the recovery of muscle mass via either satellite cell activation or transcriptional control. Each hypothesis will be tested by: i) employing time-course analyses; ii) sterilizing satellite cells via irradiation; iii) manipulating the duration of mechanical unloading/immobilization; iv) employing resistance training; and v) manupulating IGF-1.
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