ACTIVATION AND NOVEL PROCESSING OF MATRIX METALLOPROTEINASES BY A THIOL PROTEINASE FROM THE ORAL ANAEROBE PORPHYROMONAS-GINGIVALIS

A critical outcome of periodontal disease is degradation of the collag enous periodontal ligament that connects teeth to bone in the dental a rch. Periodontal diseases occur in response to bacterial colonization of the teeth, but their molecular pathogenesis is still speculative. O ne family of enzymes, known as the matrix metalloproteinases (MMPs), h as been implicated in the degradation of the periodontal ligament. MMP s, which are also suspected to play a role in many other physiologic a nd pathologic remodeling processes, can be secreted by epithelial cell s surrounding the teeth and are found in relative abundance in tissues and fluids near periodontally diseased sites. Since most MMPs are sec reted as inactive zymogens which may be activated by limited proteolys is, it has been suggested that proteinases expressed by the infecting periodontal pathogens might activate latent host MMPs to initiate or a ccelerate degradation of the collagenous periodontal ligament. The aim of this work was to examine interactions between purified host MMPs a nd bacterial proteinase. Ln this article, we demonstrate that a protei nase isolated from the periodontopathogen Porphyromonas gingivalis can activate MMP-1, MMP-3, and MMP-9 and can catalyze the superactivation of MMP-1 by MMP-3. Activation of these Mh?Ps is demonstrated to resul t from initital hydrolysis within their propeptide. Also, for MMP-1 an d MMP-9: the P. gingivalis proteinase cleaves the MMP propeptide follo wing a lysine residue at a previously unreported site which, for both MMPs, is one residue NH2-terminal to the known autocatalytic cleavage site. These data describe a mode of virulence for the periodontopathog en Porphyromonas gingivalis that involves activation of host-degradati ve enzymes.