Matrix metalloproteinases and A Disintegrin and Metalloproteinase with Thrombospondin motifs enzymes (MMPs and ADAMTS)

Catabolic cartilage-degrading enzymes are a functional class of proteolytic enzymes, primarily comprising Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS), that mediate the breakdown of the articular cartilage extracellular matrix (ECM). In healthy joints, these enzymes are essential for normal tissue remodeling and homeostasis, maintaining a balance between the synthesis and degradation of structural components like Type II collagen and aggrecan. However, in degenerative diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA), inflammatory cytokines (e.g., IL-1β, TNF-α) and mechanical stress trigger the pathological upregulation of these enzymes, leading to progressive and often irreversible joint destruction. MMP-13 is the primary collagenase responsible for degrading the triple helix of Type II collagen, while ADAMTS-4 and ADAMTS-5 are the major aggrecanases that cleave aggrecan, the primary proteoglycan providing cartilage with its weight-bearing properties. Therapeutic strategies have historically focused on broad-spectrum metalloproteinase inhibitors, but modern drug development shifted toward highly selective inhibitors to avoid the severe musculoskeletal toxicities associated with non-specific targeting.

Other names

Catabolic cartilage-degrading enzymesMatrix-degrading proteasesAggrecanasesCollagenasesCartilage-degrading metalloproteinasesMMPsADAMTS

Inhibition of the catalytic activity of zinc-dependent endopeptidases to prevent the cleavage of Type II collagen and aggrecan in the cartilage extracellular matrix.