Musculoskeletal soft tissue injuries represent a large portion of sports- related injuries. The frequency of occurrence of these injuries has increased rapidly over the last decade as participation in athletic activities and physical conditioning have increased in the United States. The junction between skeletal muscle cells and tendon collagen fibers has been implicated in a common type of soft tissue injury which occurs when active muscle is passively extended. These injuries apparently occur most frequently in inadequately trained participants which suggests that training and, conversely, disuse can influence the structure or physical properties of these myotendinous junctions (MTJs). This proposed investigation is directed toward elucidating the effects of exercise and disuse on the structure, molecular composition and mechanical strength of MTJs using frog skeletal muscle as a model. These experimental animals were selected because: 1) they are unusual in that single cell mechanical testing can be easily performed, and 2) the molecular composition and quantitative ultrastructure of their MTJs has been studied previously. In the proposed investigation, these animals will be subjected to strength-training, increased-frequency exercise, reduced-frequency exercise or denervation atrophy. At selected times in their training, representative animals from each group will be sacrificed and hind limb muscles analyzed for changes in: 1) mass, 2) aerobic capacity, 3) anaerobic capacity, 4) quantitative MTJ structure, 5) concentration of structural proteins at the MTJ, or 6) breaking strength at the MTJ. These data will provide the first information on the response of MTJs to exercise and disuse. These data will also provide the basis of a comprehensive description of the relationships between modifications in muscle cell structure and molecular composition to load-bearing at MTJs in ways that can be related to clinically-observed defects in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR040343-03
Application #
3160704
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1989-08-05
Project End
1993-03-31
Budget Start
1991-08-01
Budget End
1993-03-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Arts and Sciences
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Curzi, D; Lattanzi, D; Ciuffoli, S et al. (2013) Growth hormone plus resistance exercise attenuate structural changes in rat myotendinous junctions resulting from chronic unloading. Eur J Histochem 57:e37
Wehling-Henricks, Michelle; Tidball, James G (2011) Neuronal nitric oxide synthase-rescue of dystrophin/utrophin double knockout mice does not require nNOS localization to the cell membrane. PLoS One 6:e25071
Villalta, S Armando; Rinaldi, Chiara; Deng, Bo et al. (2011) Interleukin-10 reduces the pathology of mdx muscular dystrophy by deactivating M1 macrophages and modulating macrophage phenotype. Hum Mol Genet 20:790-805
Wehling-Henricks, Michelle; Jordan, Maria C; Gotoh, Tomomi et al. (2010) Arginine metabolism by macrophages promotes cardiac and muscle fibrosis in mdx muscular dystrophy. PLoS One 5:e10763
Villalta, S Armando; Nguyen, Hal X; Deng, Bo et al. (2009) Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy. Hum Mol Genet 18:482-96
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Wehling-Henricks, Michelle; Sokolow, Sophie; Lee, Jamie J et al. (2008) Major basic protein-1 promotes fibrosis of dystrophic muscle and attenuates the cellular immune response in muscular dystrophy. Hum Mol Genet 17:2280-92
Tidball, James G; Wehling-Henricks, Michelle (2005) Damage and inflammation in muscular dystrophy: potential implications and relationships with autoimmune myositis. Curr Opin Rheumatol 17:707-13
Wehling-Henricks, Michelle; Jordan, Maria C; Roos, Kenneth P et al. (2005) Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium. Hum Mol Genet 14:1921-33
Tidball, James G; Wehling-Henricks, Michelle (2004) Expression of a NOS transgene in dystrophin-deficient muscle reduces muscle membrane damage without increasing the expression of membrane-associated cytoskeletal proteins. Mol Genet Metab 82:312-20

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