Matrix metalloproteinases (MMPs) represent a major group of enzymes that regulate cell-matrix composition. MMPs are produced by a number of cell types, including fibroblasts, macrophages, endothelial cells, and keratinocytes. The function of MMPs is not only the degradation of the extracellular matrix (ECM) and the basal membrane, as MMPs are also considered signalling proteases - tissue inhibitors of metalloproteinases (TIMPs) can activate granulocytes and are able to protect inflammatory cells from apoptosis. The collagenases (MMP 1,8,13,18) are capable of degrading triple-helical fibrillar collagens into distinctive 3/4 and 1/4 fragments. These collagens are the major components of bone, cartilage, and dentin, and MMPs are the only known mammalian enzymes capable of degrading them. The main substrates of the gelatinases (MMP 2, MMP 9) are type IV collagen and gelatin. MMP-2 degrades not only extracellular matrix proteins (collagen type I, III, IV, V, VII, X, XI, gelatin, elastin, ecorin, aggrecan, fibronectin, laminin, tenascin and vitronectin) but also several nonmatrix proteins such as interleukin 1 beta, protransforming growth factor beta (pro-TGFβ), pro-tumour necrosis factor (pro-TNF), among others. Stromelysins (MMP 3,10,11) display a broad ability to cleave extracellular matrix proteins.

Under physiological conditions, MMPs are involved in the homeostasis of tissues, angiogenesis, bone remodelling, and wound healing. Moreover, MMPs modulate the immune and inflammatory response, tumour invasion, and contribute to atherosclerotic plaque rupture. Dysregulation of MMPs function is observed in human pathology, for example, in arthritis, inflammation, and cancer. Thermal injury causes upregulation of MMPs leading to degradation of the basal lamina, detrimental swelling of surrounding tissues, and increased blood-brain barrier permeability and brain oedema. MMPs and tissue inhibitors of metalloproteinases (TIMPs) have also been evaluated extensively in sepsis. MMPs have been long considered and declined as therapeutic targets, but late evidence suggests their revival.

The aim of this Special Issue is to gather papers investigating the roles of matrix metalloproteinases in human pathology and physiology. We welcome both original research and review articles looking at the roles of MMPs in a range of diseases and conditions and associated immune responses, as well as their potential as therapeutic targets.

Potential topics include but are not limited to the following:

• The role of MMPs in trauma, tissue injury, and wound healing
• The role of MMPs and TIMPs in inflammatory diseases
• The importance of MMPs in the physiology and diseases of bone tissue
• The role of MMPs in neoplastic diseases
• The role of MMPs and TIMPs in immune response
• The importance of MMPs in angiogenesis
• The potential role of MMPs and TIMPs as therapeutic targets
• The role of MMPs in cartilage homeostasis and in the regulation of chondrocyte catabolism
• The role of MMPs in rheumatic diseases and in osteoarthritis