Aggrecanase

"Aggrecanases" are extracellular metalloproteinases responsible for cleaving the core protein of aggrecan at specific sites within articular cartilage. The two principal human aggrecanases are ADAMTS‑4 (aggrecanase‑1) and ADAMTS‑5 (aggrecanase‑2). These enzymes play a central role in cartilage breakdown during osteoarthritis by degrading the highly charged proteoglycans that provide compressive strength to joint tissues. Loss or excessive activity leads to depletion of functional aggrecans from articular cartilage—a hallmark event early in osteoarthritic disease progression. Because they mediate this critical step, selective inhibition has been pursued as a therapeutic strategy for chondroprotection. However, clinical translation has proven challenging due to issues with selectivity, efficacy endpoints, and potential safety concerns related to broad metalloproteinase inhibition.

Other names

Aggrecan-degrading enzymeAggrecanase-1 (for ADAMTS-4)Aggrecanase-2 (for ADAMTS-5)Cartilage aggrecan endopeptidases

Inhibitors block the enzymatic activity that cleaves specific sites on the aggrecan core protein, thereby preventing loss of cartilage matrix integrity in diseases like osteoarthritis.