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Am J Pathol. 2014 Feb;184(2):472-82. doi: 10.1016/j.ajpath.2013.10.018. Epub 2013 Nov 21.

Rac-null leukocytes are associated with increased inflammation-mediated alveolar bone loss.

Author information

1
Department of Periodontology, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
2
Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada.
3
Department of Periodontology, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. Electronic address: michael.glogauer@utoronto.ca.

Abstract

Periodontitis is characterized by altered host-biofilm interactions that result in irreversible inflammation-mediated alveolar bone loss. Genetic and epigenetic factors that predispose to ineffective control of biofilm composition and maintenance of tissue homeostasis are not fully understood. We elucidated how leukocytes affect the course of periodontitis in Rac-null mice. Mouse models of acute gingivitis and periodontitis were used to assess the early inflammatory response and patterns of chronicity leading to loss of alveolar bone due to inflammation in Rac-null mice. Leukocyte margination was differentially impaired in these mice during attachment in conditional Rac1-null (granulocyte/monocyte lineage) mice and during rolling and attachment in Rac2-null (all blood cells) mice. Inflammatory responses to subgingival ligatures, assessed by changes in peripheral blood differential leukocyte numbers, were altered in Rac-null compared with wild-type mice. In response to persistent subgingival ligature-mediated challenge, Rac-null mice had increased loss of alveolar bone with patterns of resorption characteristic of aggressive forms of periodontitis. These findings were partially explained by higher osteoclastic coverage of the bone-periodontal ligament interface in Rac-null compared with wild-type mice. In conclusion, this study demonstrates that leukocyte defects, such as decreased endothelial margination and tissue recruitment, are rate-limiting steps in the periodontal inflammatory process that lead to more aggressive forms of periodontitis.

PMID:
24269593
DOI:
10.1016/j.ajpath.2013.10.018
[Indexed for MEDLINE]
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