Articular cartilage and changes in arthritis: matrix degradation

Abstract

While many proteases in articular cartilage have been described, current studies indicate that members of two families of metalloproteases - MMPs and the ADAMTSs - are responsible for the degradation of the major components of this tissue. Collagenases (MMPs) make the first cleavage in triple-helical collagen, allowing its further degradation by other proteases. Aggrecanases (ADAMTSs), in conjunction with other MMPs, degrade aggrecan, a component of the proteoglycan aggregate. Antineoepitope antibodies that recognize the cleavage products of collagen and aggrecan generated by these enzymes are now available and are being used to detect the sites of action and to quantitate degradation products.

Figure 1

Schematic representation of the domain structure of the matrix metalloproteinases (MMPs) associated with cartilage degradation. The sequence HEXXH is a conserved motif in this family of metalloproteases. The two histidine residues (H) are ligands for the essential zinc ion, and the side chain of the glutamic acid (E) acts as a general base for peptide bond cleavage. MMP-1, -8, and -13, collagenases; MMP-3, stromelysin; MMP-2 and -9, gelatinases; MMP-7, matrilysin; MMP-14, membrane type metalloproteinase-1

Figure 2

Schematic representation of the domain structure of ADAMTS members involved in aggrecan degradation. The conserved HEXXH motif is as in Figure 1. ADAMTS-4 and -5, aggrecanase-1 and -2; ADAMTS-1, also termed METH-1 (metalloprotease and thrombospondin domains).