Control steps for matrix degradation by matrix metalloproteinases (MMPs). Cells are initially stimulated by proinflammatory cytokines through cell surface receptors. These receptors then transfer the signal to the nucleus via a series of signal transduction pathways leading to mRNA upregulation. The MMP is synthesised and secreted in an inactive proform and requires activation by enzymic cleavage of the prodomain. Cells also produce natural inhibitors of MMPs, called tissue inhibitor of metalloproteinases (TIMPs), that inhibit the activated MMPs. Uncontrolled matrix degradation only occurs when the balance between the TIMP and the active MMP shifts in favour of degradation. MT, membrane type; TNFα, tumour necrosis factor alpha.
Catterall and Cawston Arthritis Res Ther 2003 5:12-24 doi:10.1186/ar604