Absence of avb6 Integrin is Linked to Periodontal Disease

Methods: Expression of avb6 integrin and its ligands was studied in normal and regenerating JE of human and murine gingiva using immunohistochemistry. Cytokine and bacterial regulation of avb6 integrin expression in cultured keratinocytes was studied using real-time PCR. Bone loss around molars of wild-type FVB and b6 integrin knockout mice was assessed using morphometry and high resolution radiographs. Specific antibodies against b6 integrin were used to block avb6 integrin-mediated TGFb1 activation in a rat model of periodontal disease initiation.

Results: In the present study, we observed that avb6 integrin is constitutively expressed in the healthy epithelium linking gingival epithelium to the tooth enamel (i.e. junctional epithelium). Its expression was, however, downregulated in human periodontal disease. Remarkably, integrin b6 knockout mice developed classical signs of spontaneous, chronic periodontal disease with inflammation, epithelial down-growth, pocket formation and bone loss around the teeth. Integrin avb6 acts as a major activator of TGFb1, a key anti-inflammatory regulator in the immune system. We found that TGFb1 was expressed in the healthy junctional epithelium together with avb6 integrin and that an antibody that blocks avb6 integrin-mediated activation of TGFb1 initiated inflammatory periodontal disease in a rat model.

Conclusions: Thus, avb6 integrin is constitutively expressed in the epithelium sealing the gingiva to the tooth, and it plays a central protective role against inflammatory periodontal disease via TGFb1 activation.

Acknowledgements: This study was supported by a research grant from the Canadian Institutes of Health Research.