Mast cells contribute to porphyromonas gingivalis-induced bone loss

J. Malcolm, O. Millington, E. Millhouse, L. Campbell, A. Adrados Planell, J. P. Butcher, C. Lawrence, Kirsty Ross, G. Ramage, I. B. McInnes, S. Culshaw

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 (Kit(W-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 Kit(W-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 Kit(W-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.

LanguageEnglish
Pages704-710
Number of pages7
JournalJournal of Dental Research
Volume95
Issue number6
Early online date1 Mar 2016
DOIs
Publication statusPublished - 30 Jun 2016

Fingerprint

Porphyromonas gingivalis
Mast Cells
Tumor Necrosis Factors
Bone and Bones
Periodontitis
Alveolar Bone Loss
Dysbiosis
Bacteria
Messenger RNA
Antibodies
Bone Diseases
Infection
Serum

Keywords

  • mast cells,
  • peridontitis
  • inflammation
  • mucosal immunity
  • cytokines
  • bacteria

Cite this

Malcolm, J., Millington, O., Millhouse, E., Campbell, L., Adrados Planell, A., Butcher, J. P., ... Culshaw, S. (2016). Mast cells contribute to porphyromonas gingivalis-induced bone loss. Journal of Dental Research, 95(6), 704-710. https://doi.org/10.1177/0022034516634630
Malcolm, J. ; Millington, O. ; Millhouse, E. ; Campbell, L. ; Adrados Planell, A. ; Butcher, J. P. ; Lawrence, C. ; Ross, Kirsty ; Ramage, G. ; McInnes, I. B. ; Culshaw, S. / Mast cells contribute to porphyromonas gingivalis-induced bone loss. In: Journal of Dental Research. 2016 ; Vol. 95, No. 6. pp. 704-710.
@article{19c2b10900314d7aa9943acbcd1cc5f8,
title = "Mast cells contribute to porphyromonas gingivalis-induced bone loss",
abstract = "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 (Kit(W-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 Kit(W-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 Kit(W-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.",
keywords = "mast cells, , peridontitis, inflammation, mucosal immunity, cytokines, bacteria",
author = "J. Malcolm and O. Millington and E. Millhouse and L. Campbell and {Adrados Planell}, A. and Butcher, {J. P.} and C. Lawrence and Kirsty Ross and G. Ramage and McInnes, {I. B.} and S. Culshaw",
note = "{\circledC} International & American Associations for Dental Research 2016.",
year = "2016",
month = "6",
day = "30",
doi = "10.1177/0022034516634630",
language = "English",
volume = "95",
pages = "704--710",
journal = "Journal of Dental Research",
issn = "0022-0345",
number = "6",

}

Malcolm, J, Millington, O, Millhouse, E, Campbell, L, Adrados Planell, A, Butcher, JP, Lawrence, C, Ross, K, Ramage, G, McInnes, IB & Culshaw, S 2016, 'Mast cells contribute to porphyromonas gingivalis-induced bone loss' Journal of Dental Research, vol. 95, no. 6, pp. 704-710. https://doi.org/10.1177/0022034516634630

Mast cells contribute to porphyromonas gingivalis-induced bone loss. / Malcolm, J.; Millington, O.; Millhouse, E.; Campbell, L.; Adrados Planell, A.; Butcher, J. P.; Lawrence, C.; Ross, Kirsty; Ramage, G.; McInnes, I. B.; Culshaw, S.

In: Journal of Dental Research, Vol. 95, No. 6, 30.06.2016, p. 704-710.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mast cells contribute to porphyromonas gingivalis-induced bone loss

AU - Malcolm, J.

AU - Millington, O.

AU - Millhouse, E.

AU - Campbell, L.

AU - Adrados Planell, A.

AU - Butcher, J. P.

AU - Lawrence, C.

AU - Ross, Kirsty

AU - Ramage, G.

AU - McInnes, I. B.

AU - Culshaw, S.

N1 - © International & American Associations for Dental Research 2016.

PY - 2016/6/30

Y1 - 2016/6/30

N2 - 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 (Kit(W-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 Kit(W-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 Kit(W-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.

AB - 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 (Kit(W-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 Kit(W-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 Kit(W-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.

KW - mast cells,

KW - peridontitis

KW - inflammation

KW - mucosal immunity

KW - cytokines

KW - bacteria

UR - http://jdr.sagepub.com/content/by/year

U2 - 10.1177/0022034516634630

DO - 10.1177/0022034516634630

M3 - Article

VL - 95

SP - 704

EP - 710

JO - Journal of Dental Research

T2 - Journal of Dental Research

JF - Journal of Dental Research

SN - 0022-0345

IS - 6

ER -

Malcolm J, Millington O, Millhouse E, Campbell L, Adrados Planell A, Butcher JP et al. Mast cells contribute to porphyromonas gingivalis-induced bone loss. Journal of Dental Research. 2016 Jun 30;95(6):704-710. https://doi.org/10.1177/0022034516634630