Figure 3

Nonsteroidal anti-inflammatory drug (NSAID) and steroidal anti-inflammatory drug (SAID) response signatures in human chondrocytes. Centroid view (fold change) of rheumatoid arthritis (RA)-related chondrocyte gene expression following treatment of rheumatoid arthritis synovial fibroblasts (RASFs) with (a) NSAIDs piroxicam and diclofenac and (b) SAIDs methylprednisolone and prednisolone. Black bars represent the RA-related gene expression in human chondrocytes (differential gene expression of RASFsn-stimulated chondrocytes versus NDSFsn stimulation). Grey bars represent the NSAID/SAID response signatures in human chondrocytes (differential gene expression of human chondrocytes stimulated with drug-treated RASFs compared with stimulation with untreated RASFs). Whereas piroxicam mainly influenced the expression of RA-related genes involved in inflammation/nuclear factor-kappa-B (NF-κB) and cytokines/chemokines, diclofenac predominantly had an impact on the expression of genes associated with immune response. Expression of numerous RA-related genes was not influenced by NSAID treatment. In contrast, SAID treatment led to an almost complete reversion of chondrocyte RA-related gene expression. The expression of distinct genes involved in inflammation and cytokines/chemokines (BCL2-A1, COX-2, CXCL-8/IL-8, and IL-6) was strongly repressed. NDSFsn, supernatant of untreated healthy donor synovial fibroblast; RASFsn, supernatant of untreated rheumatoid arthritis synovial fibroblast.