Biological role of matrix metalloproteinases: a critical balance

Matrix metalloproteinases (MMPs) are members of the metzincin group of proteases which share the conserved zinc-binding motif in their catalytic active site. It was originally thought that their main function is to degrade the various components of the extracellular matrix (ECM), yet recent studies have led us to appreciate their significance as regulators of extracellular tissue signalling networks. Due to the broad spectrum of their substrate specificity, MMPs contribute to the homeostasis of many tissues and participate in several physiological processes, such as bone remodelling, angiogenesis, immunity and wound healing. MMP activity is tightly controlled at the level of transcription, pro-peptide activation and inhibition by tissue inhibitors of MMPs. Dysregulated MMP activity leads to pathological conditions such as arthritis, inflammation and cancer, thus highlighting MMPs as promising therapeutic targets. Analysis of MMP mutant mice has proved to be an essential tool for the identification of novel functions and interactions of single MMP members. Advancing our understanding of the MMP contribution to tissue homeostasis will lead us to identify causal relationships between their dysregulation and the development of disease pathologies, thus guiding us to successful MMP-directed therapies.