Mast cells contribute to Porphyromonas gingivalis–induced bone loss

Malcolm, J. et al. (2016) Mast cells contribute to Porphyromonas gingivalis–induced bone loss. Journal of Dental Research, 95(6), pp. 704-710. (doi: 10.1177/0022034516634630) (PMID:26933137)

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Periodontitis is a chronic inflammatory and bone-destructive disease. Development of periodontitis is associated with dysbiosis of the microbial community, which may be caused by periodontal bacteria, such as Porphyromonas gingivalis. Mast cells are sentinels at mucosal surfaces and are a potent source of inflammatory mediators, including tumor necrosis factors (TNF), although their role in the pathogenesis of periodontitis remains to be elucidated. This study sought to determine the contribution of mast cells to local bone destruction following oral infection with P. gingivalis. Mast cell–deficient mice (KitW-sh/W-sh) were protected from P. gingivalis–induced alveolar bone loss, with a reduction in anti–P. gingivalis serum antibody titers compared with wild-type infected controls. Furthermore, mast cell–deficient mice had reduced expression of Tnf, Il6, and Il1b mRNA in gingival tissues compared with wild-type mice. Mast cell–engrafted KitW-sh/W-sh mice infected with P. gingivalis demonstrated alveolar bone loss and serum anti–P. gingivalis antibody titers equivalent to wild-type infected mice. The expression of Tnf mRNA in gingival tissues of KitW-sh/W-sh mice was elevated following the engraftment of mast cells, indicating that mast cells contributed to the Tnf transcript in gingival tissues. In vitro, mast cells degranulated and released significant TNF in response to oral bacteria, and neutralizing TNF in vivo abrogated alveolar bone loss following P. gingivalis infection. These data indicate that mast cells and TNF contribute to the immunopathogenesis of periodontitis and may offer therapeutic targets.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Ramage, Professor Gordon and Malcolm, Dr Jennifer and Millhouse, Dr Emma and Culshaw, Professor Shauna and Adrados Planell, Miss Ana
Authors: Malcolm, J., Milington, O., Millhouse, E., Campbell, L., Adrados Planell, A., Butcher, J.P., Lawrence, C., Ross, K., Ramage, G., McInnes, I.B., and Culshaw, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Journal of Dental Research
Journal Abbr.:J Dent Res
Publisher:SAGE Publications
ISSN (Online):1544-0591
Published Online:01 March 2016

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
535611Gums and JointsShauna CulshawEuropean Commission (EC)261460SM - DENTAL SCHOOL
656691Investigating the immune response to citrullinated antigenShauna CulshawArthritis Research UK (ARUK)20823SM - DENTAL SCHOOL