HUMAN SHOULDER TENDON BIOPSY SAMPLES IN ORGAN-CULTURE PRODUCE PROCOLLAGENASE AND TISSUE INHIBITOR OF METALLOPROTEINASES

Objective-To investigate the production of the matrix metalloproteinas e (MMP), collagenase (MMP-1), and its natural inhibitor, the tissue in hibitor of metallo-proteinases (TIMP) by diseased human tendon samples in organ culture. Methods-Portions of tendons were excised from the s houlders of patients undergoing shoulder surgery, classified as either proximal to the lesion (abnormal) or distal to the lesion (normal) ac cording to their macroscopic appearance at surgery, and placed in orga n 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 var ied between patients, but in most of them TIMP levels were greater tha n collagenase levels. In one sample of calcified tendon, procollagenas e levels were greater than those of TIMP. The mean level of collagenas e produced by tendon proximal to the lesion and tendon distal to the l esion 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 bl otting and collagen fragment analysis confirmed that the collagenolyti c activity detected was attributable to the metallo-proteinase fibrobl ast collagenase (MMP-1). Conclusions-Tendon tissue can actively secret e procollagenase, an enzyme that, once activated, is capable of remode lling collagen, the major connective tissue component of tendon. Colla genase is produced even in unstimulated cultures, although the concent rations of TIMP are usually greater than that of collagenase in most s amples. Some activation of collagenase appeared to have occurred. Thes e results indicate that tendon tissue cells are capable of producing a remodelling response, even in end stage tendon disease.