To make the situation even more complex, aggrecans form aggregates with two other matrix components—hyaluronan and link proteins. This aggregate consists of a variable number of proteoglycan monomers, depending on the length of the hyaluronan, which are noncovalently attached to a single hyaluronan chain through the hyaluronan-binding G1 domain. This interaction is stabilized by the noncovalent association of link proteins to both the hyaluronan and the G1 domain. The typical molecular weight of such an aggregate can exceed 200 million (see the electron micrograph in Plate 2-25).
All the components of the proteoglycan aggregate are synthesized by chondroblasts and chondrocytes and are then transported by them for extracellular selfassembly. For example, the core protein is synthesized and some oligosaccharides are added in the rough endoplasmic reticulum, whereas the synthesis of remaining oligosaccharides and glycosaminoglycan chains and their subsequent sulfation occur in the Golgi apparatus. While aggrecan proteoglycans and link proteins are being assembled and secreted together, the cartilage cells are also synthesizing hyaluronan macromolecules at their plasma membranes and extruding them extracellularly. Once the aggrecan-link protein interacts with the hyaluronan in the extracellular space, the proteoglycan aggregate forms, resulting in one of the largest molecular complexes in nature.
The proteoglycan contents of articular cartilage, elastic cartilage, and fibrocartilage give these tissues many of their characteristic properties. For example, the critical mechanical properties of hyaline cartilage—resiliency and stiffness to compression—exist because the large bottlebrush macromolecular domains of the aggrecan proteoglycans sequester water. The anionic charges on the sulfated glycosaminoglycan chains cause them to repel one another, which expands the aggrecan domains. The concentration of aggrecan molecules within the collagen matrix prevents them from fully expanding, and they often occupy as little as one fifth of their fully expanded domains. This greatly increases the concentration of negative charges within their domain, which increases their swelling pressure due to anionic charge repulsion. This allows the cartilage to resist compressive loads with less net changes in aggrecan matrix volume per compressive load and to expand to their original compressed volume when the load is released.
The result is an efficient composite structure in which the collagen molecules form a fibrillar network that resists tensile loads and restrains the compressed aggrecan proteoglycans, which in turn resist the variable compressive loads that cartilages undergo during their normal physiological functions. Because cartilage is avascular, diffusion of nutrients and exchange of waste products occur through the tissue fluid that is mostly maintained within the aggrecan domains, which allow relatively free exchanges with the water and solutes of synovial fluid.
< div class='tao-gold-member'>