EXTRACTS OF HUMAN ARTICULAR-CARTILAGE CONTAIN AN INHIBITOR OF TISSUE METALLOPROTEINASES

When human articular cartilage is extracted with 2M-guanidinium hydrochloride at pH 7.5, an inhibitor is obtained that blocks the activity of 3 metalloproteinases, including collagenase. Molecular-sieve chromatography of the inhibitor gives an MW value for the inhibitor of 28,500. The inhibitor is stable to heat (60.degree. C, 1 h) and acid (pH2, 24.degree. C, 10 min). It is destroyed by trypsin and by reduction and alkylation. It is slowly inactivated by aminophenylmercuric acetate. It binds to concanavalin A-Sepharose and is eluted with .alpha.-D-1-O-methyl glucopyranoside. Complexes of enzyme and inhibitor are not re-activated by aminophenylmercuric acetate and only partially so by high levels of trypsin. This inhibitor apparently is a member of the TIMP (tissue inhibitor of metalloproteinases) class. Such an inhibitor, previously found in tissue culture and amniotic fluid, is now shown to be directly extractable from tissue.