Published online before print April 1, 2008

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Copyright © 2008 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2008.071068

Accepted for publication February 7, 2008.

Article

Absence of v6 Integrin Is Linked to Initiation and Progression of Periodontal Disease

Farzin Ghannad^*, Daniela Nica^*, Maria I. Garcia Fulle^*, Daniel Grenier, Edward E. Putnins^*, Sarah Johnston^*, Ameneh Eslami^*, Leeni Koivisto^*, Guoqiao Jiang^*, Marc D. McKee, Lari Häkkinen^*, and Hannu Larjava^*@

From the Laboratory of Periodontal Biology,* Faculty of Dentistry, University of British Columbia, Vancouver; the Faculty of Dentistry and Medicine, University of Laval, Montreal; and the Faculty of Dentistry and Department of Anatomy and Cell Biology, McGill University, Montreal, Canada

^@ To whom correspondence should be addressed. E-mail: larjava{at}interchange.ubc.ca.

	Abstract

Integrin v6 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 v6 integrin is constitutively expressed in the healthy junctional epithelium linking the gingiva to tooth enamel. Moreover, expression of v6 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 6 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 v6 acts as a major activator of transforming growth factor-1 (TGF-1), a key anti-inflammatory regulator in the immune system. Co-expression of TGF-1 and v6 integrin was observed in the healthy junctional epithelium. Moreover, an antibody that blocks v6 integrin-mediated activation of TGF-1 initiated inflammatory periodontal disease in a rat model of gingival inflammation. Thus, v6 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-1.