Lipopolysaccharide-induced epithelial monoamine oxidase mediates alveolar bone loss in a rat chronic wound model

Daisuke Ekuni, James D. Firth, Tarun Nayer, Takaaki Tomofuji, Toshihiro Sanbe, Koichiro Irie, Tatsuo Yamamoto, Takashi Oka, Zhenzi Liu, Juergen Vielkind, Edward E. Putnins

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21 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) production is an antimicrobial response to pathogenic challenge that may, in the case of persistent infection, have deleterious effects on the tissue of origin. A rat periodontal disease model was used to study ROS-induced chronic epithelial inflammation and bone loss. Lipopolysaccharide (LPS) was applied for 8 weeks into the gingival sulcus, and histological analysis confirmed the onset of chronic disease. Junctional epithelium was collected from healthy and diseased animals using laser-capture microdissection, and expression microarray analysis was performed. Of 19,730 genes changed in disease, 42 were up-regulated ≥4-fold. Three of the top 10 LPS-induced genes, monoamine oxidase B (MAO/B) and flavin-containing monooxygenase 1 and 2, are implicated in ROS signaling. LPSassociated induction of the ROS mediator H2O2, as well as MAO/B and tumor necrosis factor (TNF)-α levels were validated in the rat histological sections and a porcine junctional epithelial cell culture model. Topical MAO inhibitors significantly counteracted LPS-associated elevation of H 2O2 production and TNF-α expression in vivo and in vitro, inhibited disease-associated apical migration and proliferation of junctional epithelium and inhibited induced systemic H2O2 levels and alveolar bone loss in vivo. These results suggest that LPS induces chronic wounds via elevated MAO/B-mediated increases in H2O 2 and TNF-α activity by epithelial cells and is further associated with more distant effects on systemic oxidative stress and alveolar bone loss.

Original languageEnglish
Pages (from-to)1398-1409
Number of pages12
JournalAmerican Journal of Pathology
Volume175
Issue number4
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Ekuni, D., Firth, J. D., Nayer, T., Tomofuji, T., Sanbe, T., Irie, K., Yamamoto, T., Oka, T., Liu, Z., Vielkind, J., & Putnins, E. E. (2009). Lipopolysaccharide-induced epithelial monoamine oxidase mediates alveolar bone loss in a rat chronic wound model. American Journal of Pathology, 175(4), 1398-1409. https://doi.org/10.2353/ajpath.2009.090108