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Figure 4 | Arthritis Research & Therapy

Figure 4

From: Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration

Figure 4

Hierarchical clustering and principal components analyses of rheumatoid arthritis (RA)-related chondrocyte gene expression levels in response to antirheumatic treatment. Hierarchical clustering and principal components analyses of mean expression values of RA-related chondrocyte genes were performed for the 'diseased' status (RASFsn-stimulated), the 'healthy' status (NDSFsn-stimulated), and the drug-treated 'diseased' status (RASFsn antirheumatic drug-stimulated). (a) Hierarchical clustering analysis (tree plot). Colours represent relative levels of gene expression: bright red indicates the highest level of expression, and bright green indicates the lowest level of expression. Hierarchical clustering analysis showed that treatment with disease-modifying antirheumatic drugs (DMARDs) methotrexate, azathioprine, and gold sodium thiomalate resulted in chondrocyte expression patterns that were closely related to the 'healthy' status. Chloroquine phosphate and diclofenac treatment had only minor effects because they clustered together with RASFsn-stimulated chondrocytes ('diseased' status). Steroidal anti-inflammatory drug (SAID) treatment reverted the expression of some RA-related genes even beyond the 'healthy' level. (b) Principal components analysis (three-dimensional plot) demonstrates the quantitative differences of drug response. DMARDs, except for chloroquine phosphate, and SAIDs reduced the distance between RASFsn and NDSFsn stimulation to a minor difference, whereas DMARDs located toward the 'diseased' status and SAIDs reverted beyond the location of the 'healthy' status. aza, azathioprine; chloro, chloroquine phosphate; diclo, diclofenac; gold, gold sodium thiomalate; mpred, methylprednisolone; MTX, methotrexate; NDSFsn, supernatant of untreated healthy donor synovial fibroblast; NF-κB, nuclear factor-kappa-B; piro, piroxicam; pred, prednisolone; RASFsn, supernatant of untreated rheumatoid arthritis synovial fibroblast.

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