Articular cartilage: tissue design and chondrocyte-matrix interactions

Abstract

The unique biologic and mechanical properties of articular cartilage depend on the design of the tissue and the interactions between the chondrocytes and the matrix that maintain the tissue. Chondrocytes form the macromolecular framework of the tissue matrix from three classes of molecules: collagens, proteoglycans, and noncollagenous proteins. Type II, IX, and XI collagens form a fibrillar meshwork that gives the tissue as form and tensile stiffness and strength. Type VI collagen forms part of the matrix immediately surrounding the chondrocytes and may help the chondrocytes to attach to the macromolecular framework of the matrix. Large aggregating proteoglycans (aggrecans) give the tissue its stiffness to compression and its resilience and contribute to its durability. Small proteoglycans, including decorin, biglycan, and fibromodulin, bind to other matrix macromolecules and thereby help to stabilize the matrix. They may also influence the function of the chondrocytes and bind growth factors. Anchorin CII, a noncollagenous protein, appears to help to anchor chondrocytes to the matrix. Cartilage oligomeric protein may have value as a marker of turnover and degeneration of cartilage, and other noncollagenous proteins, including tenascin and fibronectin, can influence interactions between the chondrocytes and the matrix. The matrix protects the cells from injury due to normal use of the joint, determines the types and concentrations of molecules that reach the tells and helps to maintain the chondrocyte phenotype. Throughout life, the tissue undergoes continual internal remodeling as the cells replace matrix macromolecules lost through degradation. The available evidence indicates that normal matrix turnover depends on the ability of chondrocytes to detect alterations in the macromolecular composition and organization of the matrix, including the presence of degraded molecules, and to respond by synthesizing appropriate types and amounts of new molecules. In addition, the matrix acts as a signal transducer for the cells. Loading of the tissue due to use of the joint creates mechanical, electrical, and physicochemical signals that help to direct the synthetic and degradative activity of chondrocytes. A prolonged severe decrease in the use of the joint leads to alterations in the composition of the matrix and eventually to loss of tissue structure and mechanical properties, whereas use of the joint stimulates the synthetic activity of chondrocytes and possibly the internal tissue remodeling Aging leads to alterations in the composition of the matrix and the activity of the chondrocytes, including the ability of the cells to respond to a variety of stimuli such as growth factors. These alterations may increase the probability of degeneration of the cartilage.