CYTOKINE INDUCIBLE MATRIX METALLOPROTEINASE EXPRESSION IN IMMORTALIZED RAT CHONDROCYTES IS INDEPENDENT OF NITRIC-OXIDE STIMULATION

The objective of this study was to determine if an immortalized mammal ian chondrocyte cell line had a profile of matrix metalloproteinase (M MP) expression that was consistent with what has been reported for pri mary chondrocytes in vitro and in, vivo. A combination of zymography, Western, and Northern analysis was used to examine the expression of M MPs that are relevant to cartilage degradation. Both interleukin-1 bet a and tumor necrosis factor alpha induced a 4- to B-fold increase in t he level of MMP-9 expression in conditioned media, and a 17- to 24-fol d increase in MMP-3 mRNA. Other compounds such as basic fibroblast gro wth factor and staurosporine each increased MMP-9 expression individua lly and potentiated the effects of the two cytokines. Transforming gro wth factor beta had no positive or inhibitory effects. N-methyl argini ne blocked the increase in nitric oxide observed following treatment w ith the cytokines but did not prevent the increased expression of MMPs . The pattern of metalloproteinase expression observed in IRC cells an d the response to cytokines is very similar to what has been reported during the pathogenesis of osteoarthritis. The IRC cells should be use ful as a model system to study basic mechanisms controlling chondrocyt e MMP expression and to identify pharmacological modulators of this pr ocess.