Science in the News
A Mouse Model for Exploring the Connection Between Gum and Heart Disease
October 08, 2015
The pathophysiology of human periodontal disease is multifaceted. It has been shown that there is downregulation of integrin αvβ6,1 which may be linked to downregulation of the anti-inflammatory cytokine transforming growth factor β1 (TGFβ1).2 A model for human periodontal disease are mice deficient in integrin αvβ6, known as Itgβ6-/-. They develop periodontal disease complete with apical migration of junctional epithelium on the teeth, periodontal inflammation, alveolar bone resorption, and deep periodontal pocket formation.3
In a recent study,4 young adult Itgβ6-/- mice were treated with antibiotics to reduce normal oral flora. Half were inoculated with formulated mix containing 109 P. gingivalis, T. denticola, T. forsythia, and F. nucleatum every third week over a period of 24 weeks. The three control groups consisted of Itgβ6-/- mice not inoculated with the bacteria mix; a cohort of inoculated wild-type mice (i.e., mice not deficient in integrin αvβ6) and a cohort of non-inoculated wild-type mice. Afterwards, the animals were sacrificed and variety of tissue samples were taken for study.
As expected, alveolar bone resorption in maxilla and mandibles was greater in Itgβ6-/- mice than in the wild-type controls. In addition, inoculated Itgβ6-/- mice were found to have significantly greater (p>0.001) bone resorption than uninfected Itgβ6-/- mice. Examination of aortic plaque found that both the plaque area and intimal thickness were greater in Itgβ6-/- than wild-type mice. However, the response to inoculation appeared to increase plaque area and intimal thickening in wild-type mice but decrease both in the Itgβ6-/- mice.
This difference between the two strains of mice may reflect a greater systemic inflammatory response of the mice lacking Itgβ6-/-. The downregulation of integrin αvβ6 in people with periodontal disease may be associated with similarly increased inflammatory responsiveness.
- Larjava H, Koivisto L, Heino J, Hakkinen L. Integrins in periodontal disease. Exp Cell Res 2014;325(2):104-10.
- Kracklauer MP, Schmidt C, Sclabas GM. TGFbeta1 signaling via alphaVbeta6 integrin. Mol Cancer 2003;2:28.
- Ghannad F, Nica D, Fulle MI, et al. Absence of alphavbeta6 integrin is linked to initiation and progression of periodontal disease. Am J Pathol 2008;172(5):1271-86.
- Velsko IM, Chukkapalli SS, Rivera-Kweh MF, et al. Periodontal pathogens invade gingiva and aortic adventitia and elicit inflammasome activation in alphavbeta6 integrin-deficient mice. Infect Immun 2015. Abstract available at: “http://iai.asm.org/content/early/2015/09/09/IAI.01077-15.abstract”. Accessed October 8, 2015.
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