Periodontal Injection of Lipopolysaccharide Promotes Arthritis Development in Mice

This study evaluated the arthritogenic effect of lipopolysaccharide (LPS) in a mouse model of periodontal disease. Periodontitis was induced in wild-type CD1 mice by nine LPS injections (10 or 50 ng) into the maxillary mucosa. Untreated mice or injected with LPS at the tail were used as controls. Two weeks after final inoculation, mice were sacrificed to collect blood, maxilla, and paw samples. Development and progression of periodontitis and arthritis were monitored using clinical assessment, micro-computed tomography (micro-CT), ultrasound (US), and histological analysis. CXCL1, IL-1β, IL-6, TNF-α, and anti-citrullinated peptide antibodies (ACPA) serum levels were determined by enzyme immunoassay. Ankle swelling and inflammation manifested after the 5th periodontal injection of 50 ng of LPS and progressed until the end of experiments. Periodontal injection of 10 ng of LPS and LPS tail injection did not induce paw changes. Therefore, the subsequent assessments were conducted only in mice periodontally injected with 50 ng of LPS. Maxillary micro-CT and histological analysis showed that LPS-induced alveolar bone resorption and vascular proliferation in periodontal tissue, but not inflammation. US and histology revealed increased joint space, leukocyte infiltration, synovial proliferation, and mild cartilage and bone destruction in the paws of mice orally injected. Cytokines and ACPA showed a trend towards an increase in LPS mice. This study shows that arthritis and periodontal disease can co-occur in wild-type mice after periodontal injection of LPS at optimal dose. Our model may be useful to improve the understanding of the mechanisms linking periodontitis and arthritis.