In rheumatoid arthritis, an active feedback loop between inciting macrophages/leukocytes and synovial fibroblasts has been proposed in which S100A4 acts in an autocrine/paracrine manner to amplify matrix degradation and apoptosis, primarily through secretion of matrix metalloproteinases (MMPs) (18, 19). The gene discussed is S100A4; the disease is rheumatoid arthritis.