Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice

Richard Niederman, T. Westernoff, C. Lee, L. L. Mark, N. Kawashima, M. Ullman-Culler, F. E. Dewhirst, B. J. Paster, D. D. Wagner, T. Mayadas, R. O. Hynes, P. Stashenko

Research output: Contribution to journalArticle

Abstract

Background: Retrospective and correlation studies suggest that early-onset periodontal disease may be due to a deficiency in phagocyte function, a pathogenic oral biofilm, and/or dysregulated gingival cytokine expression. Increased susceptibility to periodontal disease is therefore thought to result from multiple risk factors. Methods: We tested this hypothesis prospectively using P/E-selectin adhesion molecule deficient mice that mimic the human syndrome leukocyte adhesion deficiency II. Results: Our studies demonstrate that, in comparison to wild type animals, P/E-/ - mice exhibit: spontaneous, early onset alveolar bone loss which is significant by 6 weeks of age; a 10-fold elevation in bacterial colonization of their oral cavities; and elevated gingival tissue levels of the bone resorptive cytokine IL-1α. Alveolar bone loss is completely prevented by prophylactic antibiotic therapy. Conclusions: These experiments provide the first prospective evidence for the multiple risk factor hypothesis of periodontal disease, and validate the first animal model for early onset periodontitis in which both the microbiota and host response can be systematically manipulated. P/E-/- animals should be useful in testing the virulence of putative periodontal pathogens, in determining the role of host resistance factors in periodontitis, in exploring the proposed relationship(s) between infection mediated alveolar bone loss and systemic health disorders, and exploring their genetic relationships.

Original languageEnglish (US)
Pages (from-to)569-575
Number of pages7
JournalJournal of Clinical Periodontology
Volume28
Issue number6
StatePublished - Jun 2001

Fingerprint

Alveolar Bone Loss
P-Selectin
E-Selectin
Periodontal Diseases
Leukocyte-Adhesion Deficiency Syndrome
Infection
Cytokines
Aggressive Periodontitis
Wild Animals
R Factors
Periodontitis
Microbiota
Phagocytes
Biofilms
Interleukin-1
Virulence
Mouth
Animal Models
Retrospective Studies
Anti-Bacterial Agents

Keywords

  • Adhesion molecules
  • Bacteria
  • Cytokines
  • Infectious immunity
  • Transgenic/knockout

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Niederman, R., Westernoff, T., Lee, C., Mark, L. L., Kawashima, N., Ullman-Culler, M., ... Stashenko, P. (2001). Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice. Journal of Clinical Periodontology, 28(6), 569-575.

Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice. / Niederman, Richard; Westernoff, T.; Lee, C.; Mark, L. L.; Kawashima, N.; Ullman-Culler, M.; Dewhirst, F. E.; Paster, B. J.; Wagner, D. D.; Mayadas, T.; Hynes, R. O.; Stashenko, P.

In: Journal of Clinical Periodontology, Vol. 28, No. 6, 06.2001, p. 569-575.

Research output: Contribution to journalArticle

Niederman, R, Westernoff, T, Lee, C, Mark, LL, Kawashima, N, Ullman-Culler, M, Dewhirst, FE, Paster, BJ, Wagner, DD, Mayadas, T, Hynes, RO & Stashenko, P 2001, 'Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice', Journal of Clinical Periodontology, vol. 28, no. 6, pp. 569-575.
Niederman R, Westernoff T, Lee C, Mark LL, Kawashima N, Ullman-Culler M et al. Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice. Journal of Clinical Periodontology. 2001 Jun;28(6):569-575.
Niederman, Richard ; Westernoff, T. ; Lee, C. ; Mark, L. L. ; Kawashima, N. ; Ullman-Culler, M. ; Dewhirst, F. E. ; Paster, B. J. ; Wagner, D. D. ; Mayadas, T. ; Hynes, R. O. ; Stashenko, P. / Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice. In: Journal of Clinical Periodontology. 2001 ; Vol. 28, No. 6. pp. 569-575.
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