Matrix metalloproteinases and a disintegrin and metalloproteinase with thrombospondin motifs (MMPs and ADAMTS) (MMPs and ADAMTS)

Catabolic proteases involved in cartilage matrix degradation primarily consist of matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzymes. These zinc-dependent endopeptidases are responsible for the breakdown of the extracellular matrix (ECM) in articular cartilage, a process central to the pathogenesis of osteoarthritis and rheumatoid arthritis (Troeberg & Nagase, 2012). MMP-13 (collagenase 3) is the most critical enzyme for the degradation of type II collagen, while ADAMTS-4 and ADAMTS-5 are the primary aggrecanases that cleave aggrecan, the major proteoglycan in cartilage (Burrage et al., 2006). Under physiological conditions, their activity is regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), but pathological overexpression leads to progressive joint destruction. Therapeutic efforts have shifted from broad-spectrum inhibitors, which caused dose-limiting musculoskeletal syndrome (MSS), to highly selective inhibitors targeting MMP-13 or ADAMTS-5 (Mazurek et al., 2011). Monitoring these targets often involves measuring biomarkers such as CTX-II and ARGS-aggrecan fragments in synovial fluid or serum to assess the rate of matrix turnover (Settle et al., 2010).

Other names

Cartilage-degrading proteasesAggrecanasesCollagenasesMatrix-degrading enzymesCartilage-degrading enzymes

Inhibition of the catalytic activity of zinc-dependent endopeptidases to prevent the cleavage of type II collagen and aggrecan within the articular cartilage matrix.