Molecular and cellular interactions in rheumatoid synovium

There is growing evidence that distinct molecular and cellular interactions in the rheumatoid synovium result in a complex cascade of pathophysiologic events. These interactions finally lead to progressive joint destruction, in a way that is different from all other joint diseases. Keystones are inflammation, proliferation of synovial cells, and attachment and invasion of synovial fibroblasts (in)to adjacent cartilage and bone, mediated by continuous release of matrix-degrading enzymes. Advances in molecular biology have provided numerous new data on the rheumatoid arthritis interaction cascade. Major research topics involve the balance of proinflammatory and inhibitory cytokines, the role of adhesion molecules in attachment of synovial fibroblasts to cartilage, and the localization of various matrix-degrading enzymes in the synovial lining. The results of the research reviewed here also provide a basis for future therapies including gene therapy.