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First published on May 18, 2004, doi:10.1177/0363546503262200
This version was published on July 1, 2004
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The American Journal of Sports Medicine 32:1223-1229 (2004)
© 2004 American Orthopaedic Society for Sports Medicine

Matrix Metalloproteinase and Tissue Inhibitor of Matrix Metalloproteinase mRNA Levels Are Specifically Altered in Torn Rotator Cuff Tendons

Ian K. Y. Lo, MD, FRCSC*, Linda L. Marchuk, BSc, Robert Hollinshead, MD, FRSCS, David A. Hart, PhD and Cyril B. Frank, MD, FRCSC

From the University of Calgary, Calgary, Alberta, Canada

* Address correspondence to Ian K. Y. Lo, Department of Surgery, 3330 Hospital Drive, NW, Calgary, Alberta, Canada T2N 4N1 (e-mail: ikylo{at}ucalgary.ca).

Background: Rotator cuff tears are a cause of pain and disability in the shoulder. The molecular changes associated with rotator cuff tearing are unclear. A subset of matrix metalloproteinases and tissue inhibitors of metalloproteinase, which are involved in extracellular matrix remodeling and degradation, were evaluated.

Hypothesis: There would be an increase in the mRNA level of spcific matrix metalloproteinase and a decrease in the mRNA level of specific tissue inhibitors of metalloproteinase in rotator cuff tendon tissue obtained from patients with rotator cuff tears.

Study Design: Controlled laboratory study.

Methods: Tissue was obtained from 10 patients undergoing rotator cuff repair for full-thickness rotator cuff tears. Also, tissue was obtained from cadaveric specimens with no gross evidence of rotator cuff tearing. Reverse transcription polymerase chain reaction was performed for the collagenases (MMP-1, MMP-8, MMP-13), the stromelysins (MMP-3, MMP-10, MMP-11), and the tissue inhibitors of metalloproteinase (TIMP-1, TIMP-2, TIMP-3, TIMP-4). Western blotting was performed to confirm the mRNA changes demonstrated in collagenase-3 (MMP-13).

Results: There was a significant increase in collagenase-3 (MMP-13) mRNA levels, a decrease in stromelysin-1 (MMP-3) mRNA levels, and a decrease in tisue inhibitor of metalloproteinase-2, -3, and -4 mRNA levels. Western blotting demonstrated an increase in the active form of collagenase-3 (MMP-13) in rotator cuff tendon tears.

Conclusions: The mRNA levels of specific matrix metalloproteinases and tissue inhibitors of metalloproteinase are altered in torn rotator cuff tendons.

Clinical Relevance: With the known action of the matrix metalloproteinases and tissue inhibitors of metalloproteinase in extra-cellular matrix remodeling, these findings suggest that their roles in remodeling of rotator cuff tears should be further investigated.

Key Words: matrix metalloproteinase • molecular biology • rotator cuff tear




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