Aggrecan (ACAN)

Aggrecan (ACAN) is the primary proteoglycan found in the extracellular matrix of articular cartilage, where it is essential for maintaining the tissue's structural integrity and load-bearing capacity (UniProt P16112). It functions by creating a high fixed-charge density through its glycosaminoglycan chains, which draws in water and generates the osmotic swelling pressure required to resist compression during joint movement (PubMed: 16541105). In pathological conditions such as osteoarthritis and intervertebral disc degeneration, aggrecan is targeted for degradation by specific proteases known as aggrecanases, primarily ADAMTS-4 and ADAMTS-5 (PubMed: 15647415). Therapeutic interventions aim to preserve aggrecan levels by inhibiting these enzymes or by utilizing symptomatic slow-acting drugs in osteoarthritis (SYSADOAs) like chondroitin sulfate to support matrix synthesis (PubMed: 28465309). The loss of aggrecan is a hallmark of early cartilage degeneration, making its fragments, such as the ARGS neoepitope, valuable biomarkers for monitoring disease activity and the efficacy of chondroprotective agents (PubMed: 30145264).

Other names

Cartilage proteoglycanChondroitin sulfate proteoglycan 1CSPG1Large aggregating proteoglycanAggrecan core protein

Inhibition of aggrecanase-mediated cleavage (ADAMTS-4/5) to prevent matrix depletion and supplementation of glycosaminoglycan precursors to maintain cartilage osmotic pressure.