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Journal of Clinical Periodontology

Lipopolysaccharide induces a stromal–epithelial signalling axis in a rat model of chronic periodontitis

Authors

  • James D. Firth,

    1. Department of Oral Biological & Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada
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  • Daisuke Ekuni,

    1. Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
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  • Koichiro Irie,

    1. Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
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  • Takaaki Tomofuji,

    1. Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
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  • Manabu Morita,

    1. Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan
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  • Edward E. Putnins

    Corresponding author
    • Department of Oral Biological & Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada
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  • Conflict of interest and source of funding

    The authors declare that they have no conflict of interest.

  • This research was supported by Grants-in-Aid for Scientific Research grant 18791612 to D.E. from the Ministry of Education, Culture, Sport, Science and Technology of Japan and a Canadian Institutes of Health Research grant MOP-82830 to E.P.

Address:

Edward E. Putnins

Oral Biological & Medical Sciences

Faculty of Dentistry

University of British Columbia

2199 Wesbrook Mall

Vancouver, B.C. V6T 1Z3

Canada

E-mail: putnins@dentistry.ubc.ca

Abstract

Aim

Lipopolysaccharide is a bacterial virulence factor implicated in chronic periodontitis, which may penetrate the junctional epithelial barrier and basement membrane to insult underlying stroma. We sought to identify lipopolysaccharide-induced global gene expression changes responsible for signalling between stroma and epithelium during disease onset.

Materials and Methods

Using a rat lipopolysaccharide periodontitis model, junctional epithelium and underlying stromal tissue were separately collected from healthy and diseased animals by laser-capture microdissection and subject to gene expression microarray analysis. Key gene products identified were validated in gingival epithelial and fibroblast cell cultures.

Results

Global gene expression patterns distinguishing health versus disease were found in and between both tissue types. In stroma, the most significantly altered gene ontology function group (Z ≥ 4.00) was cytokines, containing most significantly (±2-fold; p < 0.05) upregulated genes amphiregulin, IL1-β and Fas ligand, all positive, diffusible modulators of the epithelial growth factor receptor pathway. In epithelium, the most significant changes were in downregulated FOS-related antigen-1 gene, somatostatin receptor-2 gene and mucin-4 gene, all negative modulators of the epithelial growth factor receptor pathway.

Conclusion

These results establish a periodontitis model for studying gene product interactions and suggests that the onset of junctional epithelial disease hyperproliferation involves a concerted stromal–epithelial signalling axis.

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