The loss of skeletal muscle mass is of clinical importance because it is associated with increased morbidity and mortality, as well as a marked deterioration in the quality of life. A broad patient population is affected by significant losses in muscle mass including those afflicted by various systemic diseases (cancer, sepsis, HIV- AIDS), chronic physical inactivity as a result of long term bed rest, rheumatoid arthritis and limb immobilization, and sarcopenia, the age associated loss in muscle mass and strength. Satellite cells are currently an attractive therapeutic target given their stem cell characteristics and essential role in post-natal muscle growth and regeneration. What remains controversial is the necessity of satellite cells in other aspects of muscle plasticity such as hypertrophy, re-growth following atrophy and muscle maintenance with aging. In an effort to resolve this fundamental issue, a novel mouse line was created which enables the specific ablation of satellite cells in mature skeletal muscle. The Pax7-DTA mouse will be used to investigate the physiological function of satellite cells in skeletal muscle hypertrophy (Aim 1) and re-growth following muscle atrophy (Aim 2). The results from the proposed experiments are expected to provide fundamental knowledge on the function of satellite cells in adult skeletal muscle plasticity which will help define the therapeutic value of satellite cells in treating the loss of muscle mass in various clinical conditions.

Public Health Relevance

Loss of muscle, a common symptom associated with many chronic diseases, physical inactivity or aging, negatively impacts a person's quality of life, increases the susceptibility to other complications of disease and can even lead to death. Treatments designed to restore or prevent muscle loss have in part focused on using muscle stem cells referred to as satellite cells. The goal of the proposed research is to determine if satellite cells are necessary for adult muscle growth and thus, are an appropriate target for therapy for skeletal muscle loss.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MOSS-R (02))
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Boyce, Amanda T
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University of Kentucky
Physical Medicine & Rehab
Schools of Allied Health Profes
United States
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Murach, Kevin A; Fry, Christopher S; Kirby, Tyler J et al. (2018) Starring or Supporting Role? Satellite Cells and Skeletal Muscle Fiber Size Regulation. Physiology (Bethesda) 33:26-38
Murach, Kevin A; Englund, Davis A; Dupont-Versteegden, Esther E et al. (2018) Myonuclear Domain Flexibility Challenges Rigid Assumptions on Satellite Cell Contribution to Skeletal Muscle Fiber Hypertrophy. Front Physiol 9:635
Iwata, Masahiro; Englund, Davis A; Wen, Yuan et al. (2018) A novel tetracycline-responsive transgenic mouse strain for skeletal muscle-specific gene expression. Skelet Muscle 8:33
Wen, Yuan; Murach, Kevin A; Vechetti Jr, Ivan J et al. (2018) MyoVision: software for automated high-content analysis of skeletal muscle immunohistochemistry. J Appl Physiol (1985) 124:40-51
Fry, Christopher S; Kirby, Tyler J; Kosmac, Kate et al. (2017) Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy. Cell Stem Cell 20:56-69
Murach, Kevin A; Confides, Amy L; Ho, Angel et al. (2017) Depletion of Pax7+ satellite cells does not affect diaphragm adaptations to running in young or aged mice. J Physiol 595:6299-6311
Murach, Kevin A; White, Sarah H; Wen, Yuan et al. (2017) Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice. Skelet Muscle 7:14
Kirby, Tyler J; Patel, Rooshil M; McClintock, Timothy S et al. (2016) Myonuclear transcription is responsive to mechanical load and DNA content but uncoupled from cell size during hypertrophy. Mol Biol Cell 27:788-98
White, Sarah H; McDermott, Mary M; Sufit, Robert L et al. (2016) Walking performance is positively correlated to calf muscle fiber size in peripheral artery disease subjects, but fibers show aberrant mitophagy: an observational study. J Transl Med 14:284
Lee, Jonah D; Fry, Christopher S; Mula, Jyothi et al. (2016) Aged Muscle Demonstrates Fiber-Type Adaptations in Response to Mechanical Overload, in the Absence of Myofiber Hypertrophy, Independent of Satellite Cell Abundance. J Gerontol A Biol Sci Med Sci 71:461-7

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