Cartilage degradation enzymes

Cartilage degradation enzymes refer to a functional group of proteolytic enzymes, primarily matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), that are responsible for the breakdown of the articular cartilage extracellular matrix. The most critical members include Matrix metalloproteinase-13 (MMP-13), which is the primary enzyme for type II collagen degradation, and ADAMTS-4 and ADAMTS-5, which act as the major aggrecanases. In healthy joints, these enzymes are tightly regulated to maintain tissue homeostasis; however, in degenerative conditions like osteoarthritis, their pathological upregulation leads to the progressive and irreversible loss of cartilage integrity. Therapeutic development has shifted from broad-spectrum metalloproteinase inhibitors, which were limited by severe musculoskeletal side effects, toward highly selective inhibitors targeting specific enzymes like MMP-13 or ADAMTS-5. While these enzymes remain high-priority targets for disease-modifying osteoarthritis drugs (DMOADs), achieving clinical efficacy while maintaining a favorable safety profile remains a significant challenge in the field.

Other names

Matrix-degrading enzymesCartilage-degrading proteasesAggrecanases and collagenasesChondrocyte-derived proteasesMatrix metalloproteinases and ADAMTS

Inhibition of proteolytic activity to prevent the breakdown of type II collagen and aggrecan in the cartilage extracellular matrix.