Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons

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-1 3), the stromelysins (MMP-3, MMP-1 0, MMP-1 1), 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 extracellular matrix remodeling, these findings suggest that their roles in remodeling of rotator cuff tears should be further investigated.