The functional balance of metalloproteinases and inhibitors in tissue degradation: relevance to oral pathologies.
Members of the family of matrix metalloproteinases (MMPs) are key enzymes in normal and pathological tissue remodelling. They function at neutral pH and can digest synergistically all the macromolecules of the extracellular matrix. Biochemical and cloning studies indicate that there are three major groups: the specific collagenases cleave interstitial collagens; the gelatinases degrade other types of collagen and act synergistically with collagenases by degrading denatured collagens (gelatins); and the stromelysins which have broader specificity and can degrade basement membrane collagens as well as proteoglycans and matrix glycoproteins. Others in the family, but not in the major groups, are matrilysin, metallo-elastase, and several recently cloned membrane-bound metalloproteinases. Naturally occurring inhibitors, TIMPs (tissue inhibitors of metalloproteinases), are important controlling factors in the actions of MMPs, and tissue destruction in disease processes often correlates with an imbalance of MMPs over TIMPs. The relevance of recent molecular research to periodontal diseases is discussed.
Reynolds
J J
JJ
Department of Orthodontics and Paediatric Dentistry, United Medical and Dental Schools (UMDS) of Guy's Hospital, University of London, UK.
Meikle
M C
MC
D001669:Biochemical Phenomena; D001671:Biochemistry; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D053508:Matrix Metalloproteinase 12; D019278:Matrix Metalloproteinase 3 / Q000502:physiology; D020783:Matrix Metalloproteinase 7; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009059:Mouth Diseases / Q000201:enzymology / Q000209:etiology*; D009061:Mouth Mucosa / Q000201:enzymology; D010510:Periodontal Diseases / Q000201:enzymology / Q000209:etiology; D011480:Protease Inhibitors / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011509:Proteoglycans; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12