title: Human shoulder tendon biopsy samples in organ culture produce procollagenase and tissue inhibitor of metalloproteinases.
abstract: OBJECTIVE
  To investigate the production of the matrix metalloproteinase (MMP), collagenase (MMP-1), and its natural inhibitor, the tissue inhibitor of metalloproteinases (TIMP) by diseased human tendon samples in organ culture.
  
  
  METHODS
  Portions of tendons were excised from the shoulders of patients undergoing shoulder surgery, classified as either proximal to the lesion (abnormal) or distal to the lesion (normal) according to their macroscopic appearance at surgery, and placed in organ culture for periods of up to 28 days. The release of collagenase and TIMP activity in the conditioned culture medium was measured.
  
  
  RESULTS
  Procollagenase and TIMP were both produced by all the tendon samples for an extended period of time. The levels of enzyme and inhibitor varied between patients, but in most of them TIMP levels were greater than collagenase levels. In one sample of calcified tendon, procollagenase levels were greater than those of TIMP. The mean level of collagenase produced by tendon proximal to the lesion and tendon distal to the lesion were not significantly different (95.2 (SD 106.8) U/g and 34.0 (45.3) U/g, respectively), while the corresponding figures for TIMP were 109.7 (62.3) U/g and 53.0 (27.9) U/g (p = < 0.05), although there was considerable variation in some samples. Western blotting and collagen fragment analysis confirmed that the collagenolytic activity detected was attributable to the metalloproteinase fibroblast collagenase (MMP-1).
  
  
  CONCLUSIONS
  Tendon tissue can actively secrete procollagenase, an enzyme that, once activated, is capable of remodelling collagen, the major connective tissue component of tendon. Collagenase is produced even in unstimulated cultures, although the concentrations of TIMP are usually greater than that of collagenase in most samples. Some activation of collagenase appeared to have occurred. These results indicate that tendon tissue cells are capable of producing a remodelling response, even in end stage tendon disease.
authors.affiliation: North Sydney Orthopaedic and Sports Medicine Centre, Sydney, NSW, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Dalton
authors.forename: T E
authors.initials: TE
authors.lastname: Cawston
authors.forename: G P
authors.initials: GP
authors.lastname: Riley
authors.forename: I J
authors.initials: IJ
authors.lastname: Bayley
authors.forename: B L
authors.initials: BL
authors.lastname: Hazleman
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002908:Chronic Disease; D017364:Collagenases / Q000096:biosynthesis*; D046508:Culture Techniques; D004792:Enzyme Precursors / Q000096:biosynthesis*; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000201:enzymology; D017006:Rotator Cuff / Q000201:enzymology*; D012785:Shoulder Joint / Q000201:enzymology*; D019714:Tissue Inhibitor of Metalloproteinases
chemical_list: D004792:Enzyme Precursors; D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; C022440:procollagenase