title: Periodontal bacterial colonization in synovial tissues exacerbates collagen-induced arthritis in B10.RIII mice.
abstract: It has been previously hypothesized that oral microbes may be an etiological link between rheumatoid arthritis (RA) and periodontal disease. However, the mechanistic basis of this association is incompletely understood. Here, we investigated the role of periodontal bacteria in induction of joint inflammation in collagen-induced arthritis (CIA) in B10.RIII mice.
  
  
  
  CIA-prone B10.RIII mice were infected orally with a polybacterial mixture of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia for 24 weeks before induction of CIA. The ability of polybacterial mixture to colonize the periodontium and induce systemic response, horizontal alveolar bone resorption in infected B10.RIII mice was investigated. Arthritis incidence, severity of joint inflammation, pannus formation, skeletal damage, hematogenous dissemination of the infection, matrix metalloproteinase 3 (MMP3) levels, and interleukin-17 expression levels were evaluated.
  
  
  
  B10.RIII mice had gingival colonization with all three bacteria, higher levels of anti-bacterial immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies, significant alveolar bone resorption, and hematogenous dissemination of P. gingivalis to synovial joints. Infected B10.RIII mice had more severe arthritis, and higher serum matrix metalloproteinase 3 levels and activity. Histopathological analysis showed increased inflammatory cell infiltration, destruction of articular cartilage, erosions, and pannus formation. Additionally, involved joints showed had expression levels of interleukin-17.
  
  
  
  These findings demonstrate that physical presence of periodontal bacteria in synovial joints of B10.RIII mice with collagen-induced arthritis is associated with arthritis exacerbation, and support the hypothesis that oral bacteria, specifically P. gingivalis, play a significant role in augmenting autoimmune arthritis due to their intravascular dissemination to the joints.
authors.affiliation: Department of Periodontology and Oral Biology, College of Dentistry, University of Florida Gainesville, Gainesville, FL, 32610, USA.
authors.forename: Sasanka
authors.initials: S
authors.lastname: Chukkapalli
authors.affiliation: Department of Periodontology and Oral Biology, College of Dentistry, University of Florida Gainesville, Gainesville, FL, 32610, USA.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rivera-Kweh
authors.affiliation: Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
authors.forename: Prashasnika
authors.initials: P
authors.lastname: Gehlot
authors.affiliation: Department of Periodontology and Oral Biology, College of Dentistry, University of Florida Gainesville, Gainesville, FL, 32610, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Velsko
authors.affiliation: Department of Oral & Maxillofacial Diagnostic Sciences, College of Dentistry, University of Florida, Gainesville, Florida, USA.
authors.forename: Indraneel
authors.initials: I
authors.lastname: Bhattacharyya
authors.affiliation: Departments of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USA.
authors.forename: S John
authors.initials: SJ
authors.lastname: Calise
authors.affiliation: Division of Rheumatology and Clinical Immunology, College of Medicine, University of Florida, Gainesville, Florida, USA.|Department of Clinical Nursing, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Departments of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USA.
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
authors.affiliation: Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Holoshitz
authors.affiliation: Department of Periodontology and Oral Biology, College of Dentistry, University of Florida Gainesville, Gainesville, FL, 32610, USA. kesavalu@dental.ufl.edu.|Departments of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USA. kesavalu@dental.ufl.edu.
authors.forename: Lakshmyya
authors.initials: L
authors.lastname: Kesavalu
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D010518:Periodontitis / Q000150:complications* / Q000382:microbiology; D010519:Periodontium / Q000382:microbiology; D013583:Synovial Membrane / Q000382:microbiology*
keywords: B10.RIII mice; Collagen-induced arthritis; Periodontal bacteria; Periodontal disease; Porphyromonas gingivalis; Rheumatoid arthritis