Development of a convenient and sensitive assay for matrix metalloproteinase enzyme activity in synovial fluid samples using fluorigenic peptides

Abstract

Matrix metalloproteinases (MMPs) are considered to play a major role in the proteolytic degradation of extracellular matrix in joint and skeletal diseases. Inactive forms of these enzymes are secreted by cells of the joint, together with their tissue inhibitors (TIMPs). Extracellular activation results in active MMPs which can degrade most matrix components of articular cartilage such as proteoglycans and collagen proteins. Matrix degradation is inhibited by interaction of TIMPs with active MMPs. Under physiological conditions, active MMPs are efficiently neutralized, predominantly by TIMPs (MMP/TIMP ratio ≤ 1), so that net proteolytic activity is absent or very low. Under pathological conditions like in rheumatoid arthritis and osteoarthritis, levels of active MMPs as well as TIMPs are increased. More importantly, active enzymes are present in excess over the amount of tissue inhibitor (MMP/TIMP ratio>1).