Aggrecan

Aggrecan is a type of proteoglycan that is mainly found in cartilage. It is essential for the structure and function of cartilage, providing it with the ability to resist compression. Aggrecan is one of the most abundant proteoglycans in the extracellular matrix of cartilage, where it forms aggregates with hyaluronic acid and link protein, creating a highly hydrated gel structure that allows cartilage to withstand compressive forces.

Structure

Aggrecan is a large chondroitin sulfate proteoglycan with a core protein of approximately 250 kDa. The core protein consists of three globular domains (G1, G2, and G3). The G1 domain binds to hyaluronic acid, forming aggregates, the G2 domain is similar in structure to G1 but does not bind hyaluronic acid, and the G3 domain is involved in interactions with other matrix components and cell surfaces.

Function

The primary function of aggrecan is to provide cartilage with its load-bearing properties. Aggrecan molecules are highly negatively charged due to the presence of numerous sulfate and carboxyl groups on their glycosaminoglycan (GAG) chains. This negative charge attracts water molecules, creating a swelling pressure that allows cartilage to return to its original shape after being compressed.

Clinical Significance

Mutations in the aggrecan gene (ACAN) can lead to various skeletal disorders, including spondyloepiphyseal dysplasia, osteoarthritis, and Kniest dysplasia. These conditions are characterized by abnormal cartilage development, leading to joint pain and reduced mobility.

Research

Research on aggrecan is focused on understanding its role in cartilage function and pathology, as well as developing therapeutic strategies for cartilage repair and regeneration. This includes the use of aggrecan in tissue engineering applications to create synthetic cartilage substitutes.

See also

• Proteoglycan
• Cartilage
• Extracellular matrix
• Hyaluronic acid