Expression of matrix metalloproteinases (MMPs) and disintegrin metalloproteinases (ADAMs) in experimental systems of cartilage matrix degradation

Abstract

The chondrocytes of articular cartilage synthesise a number of proteinases which are capable of degrading the component molecules of this specialized extracellular matrix. The use of class-specific proteinase inhibitors indicates that major activities responsible for catabolism of proteoglycan (aggrecan) and collagen are attributable to zinc-dependent metalloproteinases. Amino acid sequence analysis of aggrecan catabolites isolated from human cartilage and synovial fluids has identified two major sites of proteolytic cleavage which occur in vivo at Asn341-Phe342 and Glu373-Ala374. Whilst cleavage at the latter site is attributed to an unknown ‘aggrecanase’, the Asn341-Phe342 bond is readily cleaved by many of the known matrix metalloproteinases. While considerable attention has focused in recent years on the expression and activity of MMPs in articular cartilage, it has now been shown (McKie et al. 1997; Patel et al. 1998) that chondrocytes can also express other metalloproteinases (e.g. the ADAM family of disintegrin-metalloproteinases, most of which have a consensus hydrophobic transmembrane sequence at their C-terminus, and many of which possess a consensus zinc-binding catalytic site which is also present in the MMPs). In this study, we have compared and quantified the mRNA expression profiles of two matrix metalloproteinases (MMP-3 and MMP-13) and five disintegrin metalloproteinases (ADAM-10, ADAM-9, ADAM-15, TNF-alpha converting enzyme and decysin) in chondrocytes (human, porcine and bovine) from fresh cartilage and in cartilage explant cultures and isolated cells cultured in monolayer or in agarose gels.