Despite the lack of a blood supply, articular cartilage chondrocytes have a high level of metabolic activity1 (Fig. 5).

Figure 5 Schematic diagram of the metabolic events controlling the proteoglycans in cartilage. The chondrocytes synthesize and secrete aggrecan, link protein and hyaluronate, and they become incorporated into functional aggregates. Enzymes released by the cells break down the proteoglycan aggregates. The fragments are released from the matrix into the synovial fluid, and from there the fragments are taken up by the lymphatics and moved into the circulating blood. (Reproduced from Mankin HJ, Mow VC, Buckwalter JA, Iannotti JP, Ratcliffe A: Articular cartilage structure, composition, and function, in Buckwalter JA, EinhornTA, Simon SR (eds): Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 443-470.)

Chondrocytes synthesize and assemble the cartilaginous matrix components and direct their distribution within the tissue. These synthetic and assembly processes involve synthesis of proteins, synthesis of glycosaminoglycan chains and their addition to the appropriate protein cores, and secretion of the completed molecules into the ECM. All of these actions take place under avascular and, at times, anaerobic conditions, with considerable variation in local mechanical, electrical and physicochemical states. In addition, the chondrocyte directs internal ECM remodeling by regulating an elaborate series of degradative enzymes. The maintenance of a normal ECM depends on three factors: (1) the ability of the chondrocytes to balance the rates of synthesis of matrix components, (2) the component’s appropriate incorporation into the matrix, and (3) the component’s degradation and release rate from the cartilage. The cells do this by responding to mechanical, electrical, and chemical stimuli in the local environments. Soluble mediators (eg, growth factors and interleukins), and changes in matrix composition, mechanical loads, and electric fields all influence the metabolic activities of the chondrocytes. The response of the chondrocytes usually will maintain a stable matrix. However, in some cases, the response of the cells can lead to a change of matrix composition and ultrastructural organization, and eventually to cartilage degeneration.