Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach

Significance Rheumatoid arthritis (RA) is an autoimmune disorder that affects ∼1% of the population. Macrophage- and fibroblast-like synoviocytes are thought to play central roles in the pathogenesis of RA. They have shared and distinct features defining RA pathology. However, these features have not been systematically explored. Using global gene expression profiling, we identified molecular signature and biological network models underlying the pathologic features of macrophage-like vs. fibroblast-like synoviocytes. Based on the network models, we selected key regulators, including POSTN and TWIST1, responsible for synoviocyte migration/invasion causing joint destruction, and their validity was experimentally confirmed. Our findings provide a comprehensive and systematic basis for mechanisms explaining RA pathogenesis and also for identification of therapeutic targets for RA.