08 August 2024

---

Researchers find mutated gene contributes to development of periodontal disease

---

Adams School of Dentistry researcher Kimon Divaris, DMD, PhD, MS, along with collaborators from the University of Pennsylvania, have found that patients diagnosed with clonal hematopoiesis of indeterminate potential (CHIP), may be more likely to develop gum disease and show higher rates of inflammation throughout the body, according to a recent study. The research was recently published in the journal Cell.

Divaris, along with Penn’s Hui Wang, studied nearly 5,000 adults and found a higher occurrence of gum disease and inflammation in patients with a specific mutation associated with CHIP called CHIP-DNMT3A. CHIP is a non-cancerous condition where certain blood cells start growing abnormally due to age-related mutations, but the patient shows no sign of hematologic disease or malignancy. These mutated cells multiply and produce changed white blood cells. The study found a link between mutations in the gene and periodontitis.

“This observation is crucial, because it emanates from a sizeable and well-characterized community-based sample of approximately 5,000 middle-aged and elderly adults and demonstrated for the first time the association between CHIP (clonal hematopoiesis of indeterminate potential) and periodontal disease,” Divaris said.

Using mouse models, the researchers transplanted bone marrow cells and found that the cells grew excessively, affecting white blood cells. This led to an increase in the cells that form bone-eating cells in the bone marrow and in the body’s inflammatory response.

In the mice receiving these mutant cells, researchers noticed an increase in naturally occurring gum disease and worsened symptoms of artificially induced gum disease and arthritis. However, researchers found that treating these mice with a drug called rapamycin helped alleviate the effects of the mutation.

This suggests that clonal hematopoiesis driven by mutations like DNMT3A might be treatable to prevent inflammatory bone diseases such as periodontitis.

“First and foremost, the elucidation of a specific mechanism linking aging with mutated stem cell clones, hyper-inflammatory states and periodontitis provides targets for mitigating this biological pathway. In this paper, we specifically demonstrate that rapamycin, an FDA-approved drug with immunosuppressant properties prevents CHIP-induced inflammatory bone loss. This immediately opens the possibility of treating periodontitis and other inflammatory bone diseases in humans in the near future,” Divaris said.

Divaris said the team science approach to this study was an ideal example of an intentional, systematic and mutually beneficial collaboration between institutions and a larger network of investigators whose expertise complemented the work.

“From our side at UNC-Chapel Hill, we were thrilled to see that our ability to interrogate large-scale human clinical and genomics data contributed to an intriguing biological story that was then elegantly demonstrated and comprehensively characterized using multi-model experimental approaches at the University of Pennsylvania.

“Besides the real-world impact of these important discoveries, it is very satisfying to experience the establishment of successful collaborative partnerships and networks that not only lead to high-impact science but also facilitate continuous learning from each other,” Divaris said.

Source: https://dentistry.unc.edu/