Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice

Background: Retrospective and correlation studies suggest that early-onset periodontal disease may be due to a deficiency in phagocyte function, a pat hogenic oral biofilm, and/or dysregulated gingival cytokine expression. Inc reased susceptibility to periodontal disease is therefore thought to result from multiple risk factors. Methods: We tested this hypothesis prospectively using PIE-selectin adhesio n molecule deficient mice that mimic the human syndrome leukocyte adhesion deficiency II. Results: Our studies demonstrate that, in comparison to wild type animals, P/E-/- mice exhibit: spontaneous, early onset alveolar bone loss which is s ignificant by 6 weeks of age; a in-fold elevation in bacterial colonization of their oral cavities; and elevated gingival tissue levels of the bone re sorptive cytokine IL-1 alpha. Alveolar bone loss is completely prevented by prophylactic antibiotic therapy. Conclusions: These experiments provide the first prospective evidence for t he multiple risk factor hypothesis of periodontal disease, and validate the first animal model for early onset periodontitis in which both the microbi ota and host response can be systematically manipulated. P/E-/- animals sho uld be useful in testing the virulence of putative periodontal pathogens, i n determining the role of host resistance factors in periodontitis, in expl oring the proposed relationship(s) between infection mediated alveolar bone loss and systemic health disorders, and exploring their genetic relationsh ips.