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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR060701-03
Application #
8317691
Study Section
Special Emphasis Panel (ZRG1-MOSS-R (02))
Program Officer
Boyce, Amanda T
Project Start
2010-09-17
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$310,284
Indirect Cost
$94,284
Name
University of Kentucky
Department
Physical Medicine & Rehab
Type
Schools of Allied Health Profes
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
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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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Jackson, Janna R; Kirby, Tyler J; Fry, Christopher S et al. (2015) Reduced voluntary running performance is associated with impaired coordination as a result of muscle satellite cell depletion in adult mice. Skelet Muscle 5:41
Fry, Christopher S; Lee, Jonah D; Mula, Jyothi et al. (2015) Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia. Nat Med 21:76-80
Kirby, Tyler J; Chaillou, Thomas; McCarthy, John J (2015) The role of microRNAs in skeletal muscle health and disease. Front Biosci (Landmark Ed) 20:37-77
Fry, Christopher S; Noehren, Brian; Mula, Jyothi et al. (2014) Fibre type-specific satellite cell response to aerobic training in sedentary adults. J Physiol 592:2625-35
Chaillou, Thomas; Kirby, Tyler J; McCarthy, John J (2014) Ribosome biogenesis: emerging evidence for a central role in the regulation of skeletal muscle mass. J Cell Physiol 229:1584-94
Su, Hai; Xing, Fuyong; Lee, Jonah D et al. (2014) Automatic Myonuclear Detection in Isolated Single Muscle Fibers Using Robust Ellipse Fitting and Sparse Representation. IEEE/ACM Trans Comput Biol Bioinform 11:714-26

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