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2013 Research Abstract

Targeted inactivation of MMP-9 in connective tissue fibroblasts to improve the regeneration of rotator cuff tears

Investigators: Max E. Davis, Jonathan P. Gumucio, Michael A. Korn, Asheesh Bedi, Christopher L. Mendias
Departments of Orthopaedic Surgery and University of Michigan, Ann Arbor

Mentor: Christopher L. Mendias, PhD

Abstract: Large tears of the rotator cuff are a common cause of shoulder pain and discomfort, this injury limits shoulder function and negatively impacts quality of life. Patients with a chronic rotator cuff tears develop fatty degeneration, shoulder pathology in which the torn rotator cuff muscles atrophy, shorten, undergo a reduction in strength, an increase in fibrosis and accumulate fat; surgical repair does not reverse fatty degeneration. Statin drugs lower lipid and cholesterol content, and this class of drugs has been shown to inhibit the activity and expression of various matrix metalloproteinases (MMPs) that are elevated in rotator cuff muscle with fatty degeneration. This study investigated the effect of simvastatin on lipid accumulation, markers of fibrosis and ECM dysfunction and overall muscle health in an animal model of fatty degeneration. Two groups of rats received a bilateral supraspinatus tenectomy, to induce fatty degeneration and subsequently received, over four weeks, a daily dose of simvastatin or vehicle. The supraspinatus muscles from each rat were removed and using histology, gene expression analysis and single-fiber contractility evaluated to discern the effect of simvastatin on muscle health and function. The rats that were treated with simvastatin experienced a decrease in the amount of visible fat, a reduction in the expression of markers for fibrosis, fat accumulation and embryonic myosin heavy chain and an increase in the specific force of muscle fibers, when compared to the supraspinatus of control rats. Simvastatin treatment improved muscle function and reduced fat accumulation in chronically torn rotator cuff muscles. The reduction in the expression of markers for fibrosis, especially MMPs and their inhibitors displays a potential etiology for fatty degeneration and suggests that improving outcomes of rotator cuff repair surgery will require further study into the effect of MMPs on the development of fatty degeneration.

Last Updated: 11/22/13

Updated on November 22, 2013.