The role of cytokines in cartilage matrix degeneration in osteoarthritis.
Chondrocytes are the single cellular component of hyaline cartilage. Under physiologic conditions, they show steady-state equilibrium between anabolic and catabolic activities that maintains the structural and functional integrity of the cartilage extracellular matrix. Implicit in the loss of cartilage matrix that is associated with osteoarthritis is that there is a disturbance in the regulation of synthetic (anabolic) and resorptive (catabolic) activities of the resident chondrocytes that results in a net loss of cartilage matrix components and deterioration in the structural and functional properties of the cartilage. Multiple mechanisms likely are involved in the disturbance of chondrocyte remodeling activities in OA. They include the development of acquired or age-related alterations in chondrocyte function, the effects of excessive mechanical loading, and the presence of dysregulated cytokine activities. Cytokines are soluble or cell-surface molecules that play an essential role in mediating cell-cell interactions. It is possible to classify the cytokines that regulate cartilage remodeling as catabolic, acting on target cells to increase products that enhance matrix degradation; as anticatabolic, tending to inhibit or antagonize the activity of the catabolic cytokines; and as anabolic, acting on chondrocytes to increase synthetic activity. This review will focus on the role of proinflammatory cytokines and their roles in mediating the increased matrix degradation that characterizes the osteoarthritic cartilage lesion.
Rheumatology Division, Beth Israel Deaconess Medical Center, Harvard Institute of Medicine, Boston, MA 02115, USA. sgoldrin@bidmc.harvard.edu
Steven R
SR
Goldring
Mary B
MB
Goldring
D000818:Animals; D002357:Cartilage Diseases / Q000209:etiology* / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D019902:Chondrocytes; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D010003:Osteoarthritis / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha