Grant: Project Grant

A large segment of the population suffers from periodontal disease (PD; gum disease) that can result in loss of teeth, a financial burden, and potentially contribute to many systemic conditions such as diabetes, cardiovascular disease, pregnancy complications, obesity, Alzheimer's disease, and even cancer. The pathogenesis of PD is a complex process in which subgingival bacterial biofilm induces inflammation that leads to tissue degradation and bone loss. In PD, pro-inflammatory cytokines are countered by anti-inflammatory cytokines. These cytokines need to be activated for biological function. An integrin known as alpha-v-beta-6 can actives them. Mutations in this integrin cause PD in mice and humans. In PD, the expression of this integrin in periodontal tissue is strongly downregulated, resulting in "acquired integrin deficiency." This integrin-mediated cytokine activation in the gingiva appears to be crucial for the maintenance of periodontal health and preventing systemic inflammation. We have discovered that epidermal growth factor receptor causes the integrin deficiency and blocking this receptor with a chemical inhibitor prevents PD in an animal model. In the present proposal, we will manufacture a slow-release formula of the inhibitor to test the hypothesis that PD can be treated by application of this inhibitor into periodontal pockets. The long-term goal is to use this formulation for the treatment of PD.