Inhibition of tissue-reparing signaling by P.gingivalis infection

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P.gingivalis, a periodontopathic Gram-negative bacteria, is known to invade into a variety of host cells such as epithelial cells and fibroblasts. A chronic inflammation of infected periodontal tissue results in tissue destruction. In this study, we investigated the involvement of the two major virulent factors of this pathogen ; fimbriae and a protease called gingipain on the destruction and inhibition of regeneration of infected host tissues.At first, we constructed fimbriae-deficient and gingipain-deficient mutants of P.gingivalis. Using these two mutants, we found that :1)Both fimbriae- and gingipain-deficient mutants of P.gingivalis showed decreased invasion in human periodontal ligament cells (PDLs).2)Infection of wild type of P.gingivalis in serum-free medium resulted in a detachment of PDLs from the culture dishes. However, gingipain-deficient mutant did not induce such detachment of PDLs.3)Infection of wild type of P.gingivalis induced a degradation of integrin-associated signaling molecules such as FAK and paxillin. However, the degradation of FAK and paxillin was not observed during infection with gingipain-deficient mutant.4)By using a scratch assay, we found that the infection of P.gingivalis strongly inhibited the regeneration of damaged monolayers of PDLs. The bacterial infection inhibited the cellular movement as well as the cellular growth.5)Gingipain-deficient mutant did not show the inhibitory effect on the regeneration of the infected cellular monolayers. On the other hand, fimbriae-deficient mutant did inhibit the regeneration process.These results strongly suggested that gingipain of P.gingivalis plays an important role in the inhibition of regeneration of the infected periodontal tissues.