ROLE OF MATRIX METALLOPROTEINASES IN HUMAN PERIODONTAL-DISEASES

MATRIX METALLOPROTEINASES (MMP) ARE A FAMILY of proteolytic enzymes th at mediate the degradation of extracellular matrix macromolecules, inc luding interstitial and basement membrane collagens, fibronectin, lami nin, and proteoglycan core protein. The enzymes are secreted or releas ed in latent form and become activated in the pericellular environment by disruption of a Zn++-cysteine bond which blocks the reactivity of the active site. The major cell types in inflamed and healthy periodon tal tissues (fibroblasts, keratinocytes, endothelial cells, and macrop hages) are capable of responding to growth factors and cytokines, as w ell as to products released from the microbial flora by induction of t ranscription of 1 or more MMP genes. Cytokines that are likely to regu late expression of MMP genes in periodontal tissues include IL-1, TNF- alpha, and TGF-alpha. In addition, triggered PMN leukocytes which expr ess only 2 MMP (PMN-CL and Mr 92K GL) release these enzymes from speci fic granule storage sites in response to a number of stimuli. The evid ence that MMP are involved in tissue destruction in human periodontal diseases is still indirect and circumstantial. Cells isolated from nor mal and inflamed gingiva are capable of expressing a wide complement o f MMP in culture and several MMP can be detected in cells of human gin giva in vivo. In addition, PMN-CL and Mr 92K GL are readily detected i n gingival crevicular fluid from gingivitis and periodontitis patients . Osteoclastic bone resorption does not appear to directly involve MMP , but a body of evidence suggests that bone resorption is initiated by removal of the osteoid layer by osteoblasts by means of a collagenase -dependent process.