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Periodontal Injection of Lipopolysaccharide Promotes Arthritis Development in Mice

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Abstract

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.

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Funding

This work was supported by Institutional Research Funds “DOR1615309/16” and “DOR1784408/17” from the University of Padova.

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Authors and Affiliations

  1. Rheumatology Unit, Department of Medicine – DIMED, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    Anna Scanu, Francesca Oliviero & Paola Galozzi

  2. Radiology Unit, Department of Medicine – DIMED, University of Padova, Padova, Italy

    Chiara Giraudo & Roberto Stramare

  3. Surgical Pathology Unit, Department of Medicine – DIMED, University of Padova, Padova, Italy

    Francesca Galuppini, Vanni Lazzarin, Gianmaria Pennelli & Massimo Rugge

  4. Department of Women’s and Children’s Health, Padova, Italy

    Francesca Galuppini

  5. Dentistry Section, Department of Neurosciences, University of Padova, Padova, Italy

    Stefano Sivolella & Edoardo Stellini

  6. Department of Surgical Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy

    Roberto Luisetto

  7. Centre for Gout and Metabolic Bone and Joint Diseases, Rheumatology, SS Giovanni and Paolo Hospital, Venice, Italy

    Leonardo Punzi

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Scanu, A., Giraudo, C., Galuppini, F. et al. Periodontal Injection of Lipopolysaccharide Promotes Arthritis Development in Mice. Inflammation 42, 1117–1128 (2019). https://doi.org/10.1007/s10753-019-00975-6

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