THE FUNCTIONAL BALANCE OF METALLOPROTEINASES AND INHIBITORS IN TISSUEDEGRADATION - RELEVANCE TO ORAL PATHOLOGIES

Members of the family of matrix metalloproteinases (MMPs) are key enzy mes in normal and pathological tissue remodelling. They function at ne utral pH and can digest synergistically all the macromolecules of the extracellular matrix. Biochemical and cloning studies indicate that th ere are three major groups: the specific collagenases cleave interstit ial collagens; the gelatinases degrade other types of collagen and act synergistically with collagenases by degrading denatured collagens (g elatins); and the stromelysins which have broader specificity and can degrade basement membrane collagens as well as proteoglycans and matri x glycoproteins. Others in the family, but not in the major groups, ar e matrilysin, metallo-elastase, and several recently cloned membrane-b ound metalloproteinases. Naturally occurring inhibitors, TIMPs (tissue inhibitors of metalloproteinases), are important controlling factors in the actions of MMPs, and tissue destruction in disease processes of ten correlates with an imbalance of MMPs over TIMPs. The relevance of recent molecular research to periodontal diseases is discussed.