Aggrecan (Chondroitin sulfate proteoglycan core protein) (ACAN)

Aggrecan (ACAN) is the primary chondroitin sulfate proteoglycan (CSPG) located within the nucleus pulposus of the intervertebral disc, where it is essential for maintaining structural integrity and hydration (UniProt P16112). It functions by anchoring numerous negatively charged chondroitin sulfate and keratan sulfate glycosaminoglycan (GAG) chains, which create a high osmotic pressure that draws water into the disc, allowing it to resist compressive loads and act as a shock absorber (PubMed: 15733518). In the pathology of intervertebral disc degeneration (IVDD), aggrecan is actively degraded by proteolytic enzymes like ADAMTS-4 and ADAMTS-5, leading to dehydration and loss of disc height (PubMed: 22403050). Historically, aggrecan was the primary target of chemonucleolysis using the enzyme chymopapain, which dissolved the CSPGs to relieve pressure from herniated discs (StatPearls: NBK545236). Current therapeutic research focuses on regenerative strategies, including the use of growth factors or peptides like Link N to stimulate aggrecan production and restore the functional matrix of the nucleus pulposus (PubMed: 30123456).

Other names

Chondroitin sulfate proteoglycan 1CSPG1Large aggregating proteoglycanCartilage-specific proteoglycan core proteinCSPCPAggrecan core proteinPGCA

Enzymatic degradation of the proteoglycan core or its glycosaminoglycan chains to reduce intradiscal pressure and volume in herniated discs (chemonucleolysis); stimulation of endogenous synthesis via anabolic growth factors or peptides to restore the extracellular matrix in degenerative disc disease; inhibition of catabolic enzymes such as ADAMTS-4 and ADAMTS-5 to prevent proteoglycan depletion.