Connective tissue degradation in health and periodontal disease and the roles of matrix metalloproteinases and their natural inhibitors.
Connective tissue remodeling is essential for normal growth and development, and many diseases have long been associated with the breakdown of the collagenous matrix of bone, cartilage, and related tissues. Recent work has established that members of the family of matrix metalloproteinases (MMPs) are key enzymes in matrix degradation. They function at neutral pH and can digest synergistically all the matrix macromolecules. Biochemical and cloning studies indicate that there are three major groups, collagenases, gelatinases, and stromelysins. 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 major inhibitor is TIMP-1 (or TIMP), a 30-kDa glycoprotein that is synthesized by most cells. The expression of MMPs and TIMPs by cells is regulated by many cytokines (particularly interleukin-1, IL-1), growth factors, and hormones, some of which are specific to cell type and others that are ubiquitous (e.g., transforming growth factor beta, TGF-beta). One way in which pathogenic organisms might mediate tissue degradation in periodontal diseases is through the ability of cell wall antigens to stimulate cytokine production by circulating mononuclear cells. These would then induce MMP synthesis by resident gingival cells, thereby initiating degradative events. Direct in vivo evidence for the source of collagenase and other MMPs in periodontal tissues is limited. By using specific polyclonal antibodies and indirect immunofluorescence, we could demonstrate the presence of collagenase, stromelysin-1, gelatinase A, and TIMP in human gingival biopsy specimens.(ABSTRACT TRUNCATED AT 250 WORDS)
Reynolds
J J
JJ
Strangeways Research Laboratory, Cambridge, UK.
Hembry
R M
RM
Meikle
M C
MC
D003238:Connective Tissue / Q000201:enzymology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005881:Gingiva / Q000201:enzymology*; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism*; D010510:Periodontal Diseases / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases