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

Am J Sports Med. Jul-Aug 2004;32(5):1223-9. doi: 10.1177/0363546503262200. Epub 2004 May 18.

Abstract

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 specific 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 tissue 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.

MeSH terms

  • Aged
  • Blotting, Western
  • Cadaver
  • Case-Control Studies
  • Collagenases / metabolism*
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3 / metabolism*
  • Middle Aged
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rotator Cuff / metabolism*
  • Rotator Cuff Injuries*
  • Tissue Inhibitor of Metalloproteinases / metabolism*

Substances

  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases
  • Collagenases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3