Sex dimorphism in periodontitis in animal models.

BACKGROUND AND OBJECTIVE: Although surveys in the USA have shown that male subjects are more prone to develop periodontitis, sex as a risk factor in periodontitis, and its mechanism, remain controversial. Animal models are ideal for investigating immunological mechanisms of sex dimorphism in periodontitis because in these models it is possible to exclude the interference of gender-related risk factors, such as smoking and oral hygiene habits. Based on surveys in humans and reports on sex dimorphism in other diseases, our hypothesis is that sex is a risk factor in periodontitis. MATERIAL AND METHODS: Different murine models (oral gavage model and ligature model) for periodontitis have been utilized to determine susceptibility to periodontitis in female and male mice. Periodontal bone levels were measured as the distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC) in young female or male mice (8-10 wk of age). Differential expression of inflammatory mediators in the gingivae of female and male mice was determined by quantitative real-time PCR. RESULTS: In comparison with male mice, female mice displayed significantly (p < 0.05) increased periodontal bone loss, accompanied by elevated expression of proinflammatory cytokines (interleukin-1ß, interleukin-6 and interleukin-17A) and higher numbers of oral bacteria. CONCLUSION: In contrast to the results in humans, in which periodontitis susceptibility is also influenced by confounding gender-related behaviors, in the murine oral gavage model and ligature model, female mice appear to be more susceptible to periodontal bone loss than male mice. In the ligature model, we observed significantly (p < 0.05) higher CEJ-ABC distance, gingival proinflammatory cytokine production and number of oral bacteria in female mice. Furthermore, our results imply that female mice develop periodontitis with a higher progression rate. Our study has therefore established that animal models can be used to dissect the mechanisms underlying genuine gender-based differences in periodontal disease susceptibility and/or progression.

Periodontal inflammation and bone loss in aged mice.

BACKGROUND AND OBJECTIVE: Young mice do not develop measurable periodontal bone loss, unless heavily infected with human periodontal pathogens. However, mice with a genetically altered immune system are unable to control their own oral flora and develop periodontitis early in life. Based on the potential of the indigenous oral microbiota to cause periodontitis, we hypothesized that normal mice may ultimately develop inflammatory periodontal bone loss, i.e. as a function of age. If confirmed, this could serve as an aging model of chronic periodontitis. MATERIAL AND METHODS: Periodontal bone levels were measured as the distance from the cementoenamel junction to the alveolar bone crest in young mice (8-10 wk of age), old mice (>or= 18 mo of age) and mice of intermediate ages. Differential expression of inflammatory mediators in the gingivae of young and old mice was determined by quantitative real-time PCR. RESULTS: In comparison with young mice, old mice displayed significantly (p < 0.05) increased periodontal bone loss, accompanied by elevated expression of proinflammatory cytokines (interleukin-1 beta, tumor necrosis factor alpha and interleukin-17A) and innate immune receptors involved in the induction or amplification of inflammation (Toll-like receptor 2, CD14, CD11b, CD18, complement C5a receptor and triggering receptor expressed on myeloid cells 3). CONCLUSION: Mice develop naturally induced periodontal bone loss as a function of age. This aging model of periodontitis represents a genuinely chronic model to study mechanisms of periodontal tissue destruction.

Differential virulence and innate immune interactions of Type I and II fimbrial genotypes of Porphyromonas gingivalis.

INTRODUCTION: The fimA-encoded fimbriae of the periodontal pathogen Porphyromonas gingivalis display genetic diversity. Type I fimbriated P. gingivalis (Pg-I) has been most widely studied at the molecular level, whereas Pg-II is the most frequent isolate from severe periodontitis. METHODS: To investigate virulence differences between Types I and II fimbriae, we examined strains 33277 (Pg-I) and OMZ314 (Pg-II), reciprocal swap mutants (i.e. expressing the heterologous fimbrial type), and their respective FimA-deficient derivatives. These organisms were tested in a mouse periodontitis model and in interactions with mouse macrophages, a cell type that plays important roles in chronic infections. RESULTS: Strain 33277 induced significantly more periodontal bone loss than OMZ314 and substitution of Type II fimbriae with Type I in OMZ314 resulted in a more virulent strain than the parent organism. However, the presence of Type II fimbriae was associated with increased proinflammatory and invasive activities in macrophages. CONCLUSION: The inverse relationship between proinflammatory potential and ability to cause experimental periodontitis may suggest that an aggressive phenotype could provoke a host response that would compromise the persistence of the pathogen.