Levels of metalloproteases and tissue inhibitor of metalloproteases in human osteoarthritic cartilage.

It is postulated that a balance is maintained between inhibitor and metalloprotease levels in normal cartilage and that in osteoarthritis increased secretion of proteases upsets this balance and results in degradation of the extracellular matrix.

Abstract

Human articular cartilage contains 2 distinct metalloproteases which degrade proteoglycan. One protease acts optimally at pH 5.3 and the other at pH 7.2. In addition, cartilage contains a tissue inhibitor of metalloproteases (TIMP) that inhibits both proteases. Methods have been developed for the estimation of metalloproteases and TIMP in extracts of cartilage prepared in buffered 2 M guanidine-HCl. In osteoarthritic cartilage, levels of the 2 metalloproteases increase 3-fold or more, while the level of TIMP remains constant. It is postulated that a balance is maintained between inhibitor and metalloprotease levels in normal cartilage and that in osteoarthritis increased secretion of proteases upsets this balance and results in degradation of the extracellular matrix.