The inhibitory effects of pro-inflammatory
cytokines interleukin-1ß (IL-1ß),
tumor necrosis factor-a (TNF-a), and
interleukin-6 (IL-6) on articular chondrocyte growth dynamics are well documented. The cartilage remodeling process is mediated entirely by chondrocytes. Most importantly, the chondrocyte is responsible not only for the synthesis of the complex extracellular matrix of the articular cartilage, but it is also the source of
proteinases and other precursors that degrade the damaged matrix to permit repair. IL-1ß and TNF-a appear to play important roles in affecting chondrocyte function. IL-1ß is extremely important to cartilage destruction contributing to increase production of
matrix metalloproteinases (MMPs) and other degradative products, while TNF-a appears to drive the inflammatory process.
IL-6 has been proposed as a contributor to the pathogenesis of
osteoarthritis. The objective of this study was to evaluate matrix degradation markers, apoptosis, cellular damage markers, and cellular morphology of chondrocytes following a challenge with these inflammatory
cytokines. Human
chondrosarcoma cells were exposed to IL-1ß, TNF-a, and
IL-6 for 24, 48, and 72 hours. Chondrocyte viability, proliferation, cellular damage, cellular function, and cellular morphology were evaluated after each time point. As early as 24 hours, chondrocytes exposed to IL-1ß and TNF-a resulted in a reduction in cell number, an increase in chondrocyte membrane damage, and a six-fold increase in MMP-13 production by chondrocytes. It was concluded that IL-1ß has the most significant effect on chondrocyte viability, proliferation and cellular function when compared to TNF-a and
IL-6.