Cellular effects of catabolic inflammatory cytokines on chondrocytes - biomed 2011

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 (MMP’s) 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.