期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 50, 期 2, 页码 -出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2022.5159
关键词
Porphyromonas gingivalis; intrapocket infection; periodontitis; gingipains; systemic inflammation
This study successfully induced local infection, including periodontitis and systemic vascular inflammation, by topically applying Pg into the gingival pockets of wild-type mice. Pathohistological changes included Pg colonization, increased gingival pocket depths, gingival inflammation, alveolar bone loss, and increased levels of pro-inflammatory cytokines in the serum.
Porphyromonas gingivalis (Pg), one of the 'red-complex' perio-pathogens known to play a critical role in the development of periodontitis, has been used in various animal models to mimic human bacteria-induced periodontitis. In order to achieve a more realistic animal model of human Pg infection, the present study investigated whether repeated small-volume topical applications of Pg directly into the gingival pocket can induce local infection, including periodontitis and systemic vascular inflammation in wild-type mice. Freshly cultured Pg was topically applied directly into the gingival pocket of the second molars for 5 weeks (3 times/week). After the final application, the mice were left in cages for 4 or 8 weeks and sacrificed. The status of Pg colony formation in the pocket, gingival inflammation, alveolar bone loss, the expression levels of pro-inflammatory cytokines in the serum and aorta, the presence of anti-Pg lipopolysaccharide (LPS) and gingipain (Kpg and RgpB) antibodies in the serum, as well as the accumulation of Pg LPS and gingipain aggregates in the gingiva and arterial wall were evaluated. The topical application of Pg into the gingival pocket induced the following local and systemic pathohistological changes in mice when examined at 4 or 8 weeks after the final topical Pg application: Pg colonization in the majority of gingival pockets; increased gingival pocket depths; gingival inflammation indicated by the increased expression of TNF-alpha, IL-6 and IL-1 beta; significant loss of alveolar bone at the sites of topical Pg application; and increased levels of pro-inflammatory cytokines, such as TNF-alpha, IL-1 beta, IL-17, IL-13, KC and IFN-gamma in the serum in comparison to those from mice receiving PBS. In addition, the Pg application/colonization model induced anti-Pg LPS and gingipain antibodies in serum, as well as the accumulation of Pg LPS and gingipain aggregates in the gingivae and arterial walls. To the best of our knowledge, this mouse model represents the first example of creating a more sustained local infection in the gingival tissues of wild-type mice and may prove to be useful for the investigation of the more natural and complete pathogenesis of the bacteria in the development of local oral and systemic diseases, such as atherosclerosis. It may also be useful for the determination of a treatment/prevention/efficacy model associated with Pg-induced colonization periodontitis in mice.
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