Figure 1

The destruction of aggrecan and therapies that slow radiographic progression of arthritis. Full-length aggrecan resides in the pericellular matrix attached to hyaluronan via link protein. Hyaluronan is bound to its cell surface receptor CD44 on articular chondrocytes. ADAMTS4 and ADAMTS5 cleavage (scissors) within the interglobular domain (IGD) of aggrecan is the most detrimental to cartilage function in arthritis as it releases the entire chondroitin sulphate (CS)-modified C-terminus into the synovium. Inhibitors of cytokine activity or ADAMTS5 may prevent cartilage loss directly. ADAMTS, A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 repeats; DMARD, disease-modifying anti-rheumatic drug; G, immunoglobulin-like domain; IL, interleukin; KS, keratan sulphate; NSAID, non-steroidal anti-inflammatory drug; TNF-α, tumor necrosis factor-alpha.