Figure 5.

Molecular pathways of rheumatoid arthritis-related cartilage destruction as reflected by the in vitro model. Illustration of differentially expressed genes of chondrocytes stimulated with supernatant of synovial fibroblast cell line derived from a patient with rheumatoid arthritis (RASFsn) compared with stimulation with supernatant of synovial fibroblast cell line derived from a normal donor (NDSFsn); induced genes were printed in bold, repressed genes in italics. Genes and text in grey are hypothetical assumptions of the established in vitro model for which further validations are still required. Cartilage destruction in rheumatoid arthritis was characterized by a disturbed homeostasis of chondrocyte function that leads to an enhanced cartilage catabolism involving extracellular matrix degradation via matrix metalloproteinases and suppressed extracellular matrix synthesis, induction of catabolic cytokines/chemokines and proinflammatory inducible enzymes, and activation of NF-κB signaling pathway. Thus, the established tissue model provided profound insights into the molecular processes involved in rheumatoid arthritis-related cartilage destruction regarding chondrocyte gene expression patterns. ADORA2A, adenosine A2A receptor; CMKOR, chemokine orphan receptor; COLL11A1, collagen type XI, α1; COMP, cartilage oligomeric matrix protein; COX, cyclooxygenase; CSPG, chondroitin sulfate proteoglycan; iNOS, inducible nitric oxide synthase; MMP, matrix metalloproteinase; NO, nitric oxide; PGs, prostaglandins; PGES, prostaglandin E synthase; RASF, synovial fibroblast cell line derived from patient with RA; RIPK, receptor-interacting serine/threonine kinase; SMS, spermine synthase; STAT, signal transduction and activators of transcription; THBS, thrombospondin; TLR, toll-like receptor; TXNIP, thioredoxin interacting protein.