Abstract
ObjectivesTo investigate the suggested role of Porphyromonas gingivalis peptidylarginine deiminase (PAD) in the relationship between the aetiology of periodontal disease and experimentally induced arthritis and the possible association between these two conditions.MethodsA genetically modified PAD-deficient strain of P. gingivalis W50 was produced. The effect of this strain, compared to the wild type, in an established murine model for experimental periodontitis and experimental arthritis was assessed. Experimental periodontitis was induced following oral inoculation with the PAD-deficient and wild type strains of P. gingivalis. Experimental arthritis was induced via the collagen antibody induction process and was monitored by assessment of paw swelling and micro-CT analysis of the radio-carpal joints. Experimental periodontitis was monitored by micro CT scans of the mandible and histological assessment of the periodontal tissues around the mandibular molars. Serum levels of anti-citrullinated protein antibodies (ACPA) and P. gingivalis were assessed by ELISA.ResultsThe development of experimental periodontitis was significantly reduced in the presence of the PAD-deficient P. gingivalis strain. When experimental arthritis was induced in the presence of the PAD-deficient strain there was less paw swelling, less erosive bone damage to the joints and reduced serum ACPA levels when compared to the wild type P. gingivalis inoculated group.ConclusionThis study has demonstrated that a PAD-deficient strain of P. gingivalis was associated with significantly reduced periodontal inflammation. In addition the extent of experimental arthritis was significantly reduced in animals exposed to prior induction of periodontal disease through oral inoculation of the PAD-deficient strain versus the wild type. This adds further evidence to the potential role for P. gingivalis and its PAD in the pathogenesis of periodontitis and exacerbation of arthritis. Further studies are now needed to elucidate the mechanisms which drive these processes.
Highlights
The endogenous microbes inhabiting humans often interact in complex ways with their hosts
Peptidylarginine deiminase is encoded on the wild type P. gingivalis genome at locus PG1424
A recombination cassette was constructed using gene splicing by Overlap Extension PCRs where the open reading frame of the ermF gene, which confers erythromycin resistance was inserted in place of the PG1424 ORF, so that ermF would be expressed from the PG1424 promoter
Summary
The endogenous microbes inhabiting humans often interact in complex ways with their hosts. In recent years periodontitis has been linked to the development of other disorders, such as coronary heart disease, diabetes mellitus and low birth weight [2]. While these associations are largely based on epidemiological evidence and for most there is currently no apparent common underlying cause, dysregulation of the inflammatory response seems to be a common underlying feature [3]. Two of the most prevalent chronic inflammatory conditions affecting humans that share many common features, including destruction of both fibrous connective tissue and bone, osteoclast activation and many common risk factors, are periodontitis and rheumatoid arthritis (RA) [4,5]
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