Although discrete triggers for arthritis remain unclear, multiple studies show that the alarmins S100A8, S100A9, Mrp8 and Mrp14 are released by phagocytes and are present in the synovial fluid, where they activate Toll-like receptor 4 to induce cytokines such as IL-1β and TNF-α (Figure 2), which in turn stimulate further matrix metalloproteinase secretion from chondrocytes [62]. This evidence concerns the gene S100A9 and Arthritis.