The Mechanism of Inflammation Caused by Oral Infection with Fusobacterium nucleatum in Periodontal Tissue

We have previously reported that oral inoculation with Fusobacterium nucleatum（F. nucleatum）caused horizontal bone resorption and increases the RANKL/OPG ratio. However, the mechanism of periodontitis induction by F. nucleatum was unknown. This study investigated how oral inoculation with F. nucleatum induced periodontitis. Mice were inoculated orally with F. nucleatum 5 times a week for 3 weeks. At day 1 or day 30 after the last oral inoculation, the animals were euthanized and subjected to histological and immunological analyses. Significant alveolar bone resorption with osteoclasts was observed in the F. nucleatum inoculation group. Inflammatory cytokines were significantly increased in gene and protein assay at day 30 after the last oral inoculation. Interestingly, F. nucleatum was detected in the serum at day 30 but not in the gingival tissue. These findings suggested that gingival inflammation might be induced via the bloodstream. Therefore, when Ca9-22 cells were added serum from F. nucleatum-inoculated mice, IL-1β was significantly observed, which was confirmed by gene and protein assays. These results suggested that F. nucleatum in blood played a central role in periodontitis caused by oral inoculation of F. nucleatum. In addition, systemic circulation of F. nucleatum was likely to contribute not only to periodontitis but also to the pathogenesis of remote organs.