Epigenetic Therapy of Periimplantitis

Over the recent sixty years, dental titanium implants have been almost universally accepted as a leading and safe system to replace lost and diseased teeth, largely due to the biological qualities of titanium to be seemingly inert to the body’s immune system. Yet, the increased longevity of patients with implants, the increased lifespan of implants within individual patients and the increased number of elderly patients with implants have exposed the number of implant failures as an everyday reality in clinical dentistry. Potential etiologic factors that contribute to peri-implantitis include oral plaque accumulation; titanium particle/ions released from dental implants, complications from implant surgery, and others. In our preliminary studies, we have successfully established a rat peri-implantitis model using immediate titanium implants in a rat mandible. We have used this model in our quest for potential mechanisms that explain peri-implantitis, including inflammation of the peri-implant environment, loss of bone and a dramatic increase in reactive oxygen species (ROS). Further studies uncovered an epigenetic mechanism through the SETD7-SFRP1-Runx2 pathway explaining titanium particle induced changes in implant bone homeostasis. Specifically, we demonstrated that both the methyltransferase Setd7 and the Wnt-inhibitor SFRP1 were upregulated in titanium-challenged PDL cells while both enrichment for H3K4me1 and Setd7 on the promoter of the SFRP1 Wnt inhibitor were increased. Together, these studies are geared to test the hypothesis that periimplantitis progresses as the result of an inflammatory microenvironment and oxidative stress and that this trend may be reversed through the application of epigenetic modulators.