Matrix metalloproteinases in inflammatory pathologies of the horse

Abstract

The extracellular matrix (ECM) of connective tissue is constantly being remodelled to allow for growth and regeneration. Normal tissue maintenance requires the ECM components to be degraded and re-synthesised in relatively equal proportions. This degradation is facilitated by matrix metalloproteinases (MMPs) and their proteolytic action is controlled primarily by the tissue inhibitors of metalloproteinases (TIMPs). Both MMPs and TIMPs exist in a state of dynamic equilibrium, with a slight excess of one or the other depending on the need for either ECM breakdown or synthesis. Long-term disruption to this balance between MMPs and TIMPs will have pathological consequences. Matrix metalloproteinases are involved in a number of diseases in mammals, including the horse. Excess MMP activity can cause ECM destruction, as seen in the lamellar basement membrane in laminitis and the articular cartilage in osteoarthritis. Matrix metalloproteinase under-activity can potentially impede healing by preventing fibrinolysis in fibrotic conditions and the removal of scar tissue in wounds. Matrix metalloproteinases also degrade non-ECM proteins and regulate cell behaviour via the release of growth factors from the substrates they cleave, increasing the scope of their effects. This review looks at the involvement of MMPs in equine health and pathologies, whilst exploring the potential consequences of therapeutic intervention.