Periodontal treatment prevents arthritis in mice and methotrexate ameliorates periodontal bone loss

• Published in: Scientific reports 2019-05, Vol.9 (1), p.8128, Article 8128
• Main Authors: Lübcke, Paul M., Ebbers, Meinolf N. B., Volzke, Johann, Bull, Jana, Kneitz, Susanne, Engelmann, Robby, Lang, Hermann, Kreikemeyer, Bernd, Müller-Hilke, Brigitte
• Format: Article
• Language: English
• Subjects: 64; 64/60; 692/4023; 692/699/1670; Alveolar bone; Alveolar Bone Loss - prevention & control; Animals; Arthritis, Experimental - microbiology; Arthritis, Experimental - prevention & control; Arthritis, Rheumatoid - microbiology; Arthritis, Rheumatoid - prevention & control; Autoantibodies; Autoantibodies - chemistry; Autoimmune diseases; Bone loss; Chlorhexidine; Chlorhexidine - pharmacology; Citrulline; Collagen; Collagen - chemistry; Computed tomography; Disease Progression; Dysbacteriosis; Enzyme-linked immunosorbent assay; Humanities and Social Sciences; Injections, Intraperitoneal; Inoculation; Male; Methotrexate; Methotrexate - pharmacology; Metronidazole; Metronidazole - pharmacology; Mice; Mice, Inbred DBA; Microbiomes; Mouthwashes; multidisciplinary; Oral administration; Peptides; Periodontitis; Periodontitis - therapy; Porphyromonas gingivalis; Relative abundance; Rheumatoid arthritis; Science; Science (multidisciplinary); Teeth; X-Ray Microtomography
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-44512-9

Recent studies indicate a causal relationship between the periodontal pathogen P . gingivalis and rheumatoid arthritis involving the production of autoantibodies against citrullinated peptides. We therefore postulated that therapeutic eradication P . gingivalis may ameliorate rheumatoid arthritis development and here turned to a mouse model in order to challenge our hypothesis. F1 (DBA/1 x B10.Q) mice were orally inoculated with P . gingivalis before collagen-induced arthritis was provoked. Chlorhexidine or metronidazole were orally administered either before or during the induction phase of arthritis and their effects on arthritis progression and alveolar bone loss were compared to intraperitoneally injected methotrexate. Arthritis incidence and severity were macroscopically scored and alveolar bone loss was evaluated via microcomputed tomography. Serum antibody titres against P . gingivalis were quantified by ELISA and microbial dysbiosis following oral inoculation was monitored in stool samples via microbiome analyses. Both, oral chlorhexidine and metronidazole reduced the incidence and ameliorated the severity of collagen-induced arthritis comparable to methotrexate. Likewise, all three therapies attenuated alveolar bone loss. Relative abundance of Porphyromonadaceae was increased after oral inoculation with P . gingivalis and decreased after treatment. This is the first study to describe beneficial effects of non-surgical periodontal treatment on collagen-induced arthritis in mice and suggests that mouthwash with chlorhexidine or metronidazole may also be beneficial for patients with rheumatoid arthritis and a coexisting periodontitis. Methotrexate ameliorated periodontitis in mice, further raising the possibility that methotrexate may also positively impact on the tooth supporting tissues of patients with rheumatoid arthritis.