Absence of alphavbeta6 integrin is linked to initiation and progression of periodontal disease.
Integrin alphavbeta6 is generally not expressed in adult epithelia but is induced in wound healing, cancer, and certain fibrotic disorders. Despite this generalized absence, we observed that alphavbeta6 integrin is constitutively expressed in the healthy junctional epithelium linking the gingiva to tooth enamel. Moreover, expression of alphavbeta6 integrin was down-regulated in human periodontal disease, a common medical condition causing tooth loss and also contributing to the development of cardiovascular diseases by increasing the total systemic inflammatory burden. Remarkably, integrin beta6 knockout mice developed classic signs of spontaneous, chronic periodontal disease with characteristic inflammation, epithelial down-growth, pocket formation, and bone loss around the teeth. Integrin alphavbeta6 acts as a major activator of transforming growth factor-beta1 (TGF-beta1), a key anti-inflammatory regulator in the immune system. Co-expression of TGF-beta1 and alphavbeta6 integrin was observed in the healthy junctional epithelium. Moreover, an antibody that blocks alphavbeta6 integrin-mediated activation of TGF-beta1 initiated inflammatory periodontal disease in a rat model of gingival inflammation. Thus, alphavbeta6 integrin is constitutively expressed in the epithelium sealing the gingiva to the tooth and plays a central role in protection against inflammatory periodontal disease through activation of TGF-beta1.
Ghannad
Farzin
F
University of British Columbia, Faculty of Dentistry, Laboratory of Periodontal Biology, 2199 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3.
Nica
Daniela
D
Fulle
Maria I Garcia
MI
Grenier
Daniel
D
Putnins
Edward E
EE
Johnston
Sarah
S
Eslami
Ameneh
A
Koivisto
Leeni
L
Jiang
Guoqiao
G
McKee
Marc D
MD
Häkkinen
Lari
L
Larjava
Hannu
H
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005881:Gingiva / Q000378:metabolism / Q000473:pathology; D005891:Gingivitis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics; D016023:Integrins / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D010510:Periodontal Diseases / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000951:Antigens, Neoplasm; D039641:Integrin beta Chains; D016023:Integrins; D053773:Transforming Growth Factor beta1; C073878:integrin alphavbeta6; C072170:integrin beta6; D020782:Matrix Metalloproteinases