Objective: Matrix metalloproteinases (MMPs) are involved in the remodelling and the turnover of periodontal tissue and are tightly regulated by tissue inhibitors of metalloproteinases (TIMPs). Disturbances in the balance between MMPs and TIMPs result in excessive tissue destruction. Using an engineered human oral mucosa (EHOM) model, we previously demonstrated that
Porphyromonas gingivalis can infiltrate into the connective tissue. The aim of this study was to investigate the regulation of MMPs and TIMPs secretion in the engineered
in vitro model infected with
P. gingivalis. Method: The EHOM model composed of normal human epithelial cells and fibroblasts was produced and infected with
P. gingivalis ATCC 33277 or a proteinase-null mutant. At 4, 8 and 24 h post-infection, tissue culture media were collected and analyzed by ELISA for MMP-2, MMP-9, TIMP-1 and TIMP-2 production. Tissues were used for histological analysis. Results: Significant tissue structural modifications following
P. gingivalis infection, more particularly with the wild type strain, were observed by optical microscopy of the EHOM sections. ELISA measurements revealed that EHOM tissue constitutively produced MMP-2, MMP-9, TIMP-1 and TIMP-2. Interestingly, increased production of these molecules was observed in the early period of infection with
P. gingivalis ATCC 33277. The levels of MMP-2 and MMP-9 increased by 4.6- and 2-fold respectively compared to basal levels. A mutant of
P. gingivalis deficient in Arg- and Lys-gingipain cysteine proteinases induced more efficiently MMPs and TIMPs production than the wild type strain. The MMPs and TIMPs production appears to be the consequence of their gene activation. Conclusion: These results suggest that
P. gingivalis up-regulates MMP production in human oral mucosa, a phenomenon that may contribute to tissue destruction. This study was supported by the Canadian Institutes of Health Research.