Aggrecan is a large molecule crucial for the structural integrity and function of various tissues, particularly cartilage. In cartilage, it enables the tissue to withstand mechanical forces. This includes providing cushioning within joints, a function heavily reliant on aggrecan’s unique properties.
What is Aggrecan
Aggrecan is a proteoglycan, a protein heavily modified with large carbohydrate chains. Its structure consists of a core protein to which numerous glycosaminoglycan (GAG) chains are attached. These GAG chains are primarily chondroitin sulfate and keratan sulfate, with approximately 100 chondroitin sulfate and up to 60 keratan sulfate chains per aggrecan molecule.
This large molecule is a main component of the extracellular matrix in articular cartilage. Articular cartilage is the smooth, white connective tissue covering bone surfaces within joints, enabling nearly frictionless movement. The highly negatively charged nature of aggrecan is a direct consequence of its numerous GAG chains.
Aggrecan’s core protein possesses three globular domains. The G1 domain specifically interacts with hyaluronan and a link protein, forming large, stable complexes within the extracellular matrix. This aggregation is a distinctive feature of aggrecan and is fundamental to its functions.
Functions of Aggrecan
The highly negatively charged glycosaminoglycan chains of aggrecan attract and trap a large amount of water within the cartilage matrix. This water-binding capacity creates a hydrated, gel-like environment, giving cartilage its unique mechanical properties. It allows the tissue to resist compression, acting as a natural shock absorber during movement and weight-bearing activities.
Aggrecan’s ability to imbibe water provides cartilage with its load-bearing properties and contributes to its viscoelasticity. This allows cartilage to resist sudden impacts and deform slowly under sustained loads. The high concentration of aggrecan in the extracellular matrix generates a swelling pressure that counters compressive forces on the tissue.
Aggrecan also contributes to the overall structural integrity of the cartilage extracellular matrix. By forming large aggregates, it creates a robust network that helps maintain the tissue’s resilience and elasticity. This structural support allows cartilage to withstand continuous mechanical stress in joints, ensuring smooth motion and cushioning between bones.
Aggrecan’s Role in Joint Health and Disease
Maintaining aggrecan’s integrity is important for long-term joint function. In healthy joints, chondrocytes, the cells within cartilage, continuously produce and maintain aggrecan. However, in various joint diseases, the balance between aggrecan synthesis and degradation can be disrupted, leading to its loss from the cartilage.
The degradation or loss of aggrecan is a hallmark event in the progression of osteoarthritis, a common joint disease. In this condition, enzymes like aggrecanases and matrix metalloproteinases (MMPs) cleave the aggrecan core protein. This enzymatic breakdown compromises the molecule’s structure, reducing its ability to bind water.
As aggrecan is degraded and lost from the cartilage, the tissue loses its water content and its ability to resist compression and absorb shock. This leads to a softening and weakening of the cartilage, making it more susceptible to damage and erosion. The progressive breakdown of cartilage in osteoarthritis results in increased friction between bones, inflammation, and pain.
Aggrecan fragments resulting from this degradation can accumulate in the synovial fluid of affected joints, indicating ongoing tissue destruction. While aggrecan turnover occurs normally, an imbalance where degradation surpasses synthesis directly contributes to the decline of joint health. Preserving aggrecan levels and function is therefore a focus in understanding and addressing joint conditions like osteoarthritis.