Tendinopathy is a progressive degeneration of the link between a skeletal muscle and its bony insertion. The shoulder is the most common site of tendinopathy, with 30% of individuals over 60 years of age experiencing rotator cuff-related injuries. Clinically, these injuries manifest as shoulder pain, weakness and stiffness, and impairments in activities of daily living. Tendinopathy is a progressive condition, so as tendon tear size and duration of injury increase, more severe atrophic changes in the muscle are observed. These changes: muscle retraction, atrophy, fibrosis, and nerve injury are associated with poor treatment outcomes, as muscles become resistant to conventional rehabilitation. Our central hypothesis is that rotator cuff tears induce a continuum of muscle atrophy and fibrosis, leading to a critical threshold, beyond which rehabilitation exercise compounds muscle fibrosis and degeneration, further impairing functional recovery. However, the biochemical, cellular, and mechanical characteristics of muscles associated with the spectrum of rotator cuff tendon tear severities are poorly defined in humans. In this proposal, our goal is to understand the structural, mechanical and physiological properties of these muscles. To achieve this goal, Specific Aim 1 will use MRI and direct tissue measurements to quantify muscle architectural changes associated with rotator cuff tears and repairs. Using tissue harvested intraoperatively, Specific Aim 2 will measure the whole muscle, muscle fascicle, and single muscle cell passive mechanical properties and protein-concentrations to identify the mechanism of increased muscle stiffness. Following a defined bout of pre-operative exercise, Specific Aim 3 will identify which patients respond to exercise with muscle hypertrophic, fibrotic, and adiopgenic expression profiles. These patients will be followed for six months post-operatively to measure strength and muscle recovery. These experiments will elucidate the structural, mechanical, physiological health and the adaptive potential of rotator cuff muscles after tendon tear. This contribution is significant because it is the first step in a continuum of research that is expecte to lead to novel exercise, pharmacological, and surgical interventions aimed at reversing atrophic muscle changes that obstruct patient recovery. The proposal is innovative, in our opinion, because it utilizes novel tissue testing and MRI methods to measure muscle structure, function, and adaptation in living humans. The absence of which has limited our understanding of atrophic muscle changes in all patients with tendinopathy. Their successful completion will have an immediate impact on the clinical treatment of rotator cuff tears because they will provide direct evidence and a non-invasive method for identifying patients who will respond and not respond to standard clinical care. In the long-term, these data will aid physical therapists in the design of unique, individualized rehabilitation strategies for patients with tendinopathy-related muscle atrophy.

Public Health Relevance

Rotator cuff injuries are associated with progressive muscle atrophy, fibrosis, and fatty infiltration. These atrophic changes are major obstacles to successful rehabilitation. These experiments aim to identify the underlying changes in muscle structure, mechanics, and adaptive potential in an effort to improve patient outcomes.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD073180-01A1
Application #
8503827
Study Section
Musculoskeletal Rehabilitation Sciences Study Section (MRS)
Program Officer
Nitkin, Ralph M
Project Start
2013-05-01
Project End
2018-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
1
Fiscal Year
2013
Total Cost
$301,481
Indirect Cost
$93,981
Name
University of California San Diego
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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