The National Institute of Dental & Craniofacial Research, part of the National Institutes of Health, has awarded a grant to researchers at New York University College of Dentistry (NYU Dentistry) to explore the biological mechanisms that contribute to poor oral health and related bone loss among people with diabetes. The grant (R01DE027074), which began April 1, provides $2.2 million over five years.
People with type 2 diabetes are prone to developing periodontitis, or inflammation of the gums and supporting structures of the teeth. The International Diabetes Federation estimates that at least 55 percent of people with diabetes will develop chronic periodontitis.
Periodontitis involves an elevated inflammatory response and greater bone resorption, or the breakdown of bone tissue, by osteoclasts. Diabetes may accelerate periodontitis through metabolic dysregulation, shifts in bacterial colonization, inflammation, and bone loss.
Because bone loss and fracture risk are serious concerns for people with diabetes, Xin Li, PhD, associate professor of basic science and craniofacial biology at NYU College of Dentistry, has been working to understand the underlying mechanism for periodontal bone loss in people with diabetes. In recent studies, including one published last year in Nature Communications, Dr. Li’s research team found that succinate, an important metabolite, is significantly elevated by high blood sugar and in type 2 diabetes patients.
Succinate activates the succinate receptor to stimulate the development of osteoclasts and bone resorption. In a study in mice, periodontal bone loss was greater in normal mice with more succinate and mitigated in mice deficient in the gene for succinate receptors.
“We hypothesize that targeting succinate signaling will prevent the acceleration of periodontal disease. Our research will test this hypothesis and reveal the underlying mechanisms of succinate actions from multiple perspectives,” said Dr. Li, the lead principal investigator of this project.
The new NIDCR grant will fund research to determine whether elevated levels of succinate accelerate the progression of periodontal disease. Using mouse models, the researchers will investigate whether succinate signaling alters the oral microbiome, study the role of succinate as an inflammatory and immune mediator, and determine whether blocking succinate signaling can thwart diabetes-related periodontal bone loss.
“Because we’ve found that succinate has significant implications for periodontal disease, we hope that by understanding this novel mechanism, we can help prevent periodontal bone loss in those with diabetes,” said Deepak Saxena, PhD, associate professor of basic science and craniofacial biology at NYU College of Dentistry and one of the project’s principal investigators.
The project is a collaboration with the University of Pennsylvania School of Dental Medicine (Penn Dental Medicine). Dana T. Graves, DDS, DMSc, interim dean of Penn Dental Medicine, is also a principal investigator.