Impact of Diabetes Hyperglycemia on Peri-Implantitis
Principal Investigator/Project Director
Colleges / Centers
College of Dental Medicine
U.S. DHHS - National Institutes of Health (NIH)
During 10 years after dental implant placement approximately 30% of patients develop peri-implantitis, a disease characterized by soft tissue infection and inflammation and bone resorption around implant. The associated socio-economic burdens are significant, and patients often suffer from the chronic and distressing symptoms. Recent studies suggested that Diabetes mellitus (DM) hyperglycemia is a risk factor of peri-implantitis. However, it is unclear how hyperglycemia contributes to the pathogenesis of peri-implantitis. Without a clear understanding of the mechanism and appropriate intervention, a large number of DM patients who receive dental implant placement will continue to face the potentially higher risk of developing peri-implantitis. Our preliminary data using a murine model of experimental peri-implantitis demonstrated that differential oral microbial compositions were observed between hyperglycemic vs. normoglycemic mice, and hyperglycemic mice showed upregulation of pro-inflammatory cytokines (IL-17 and IFNg) and greater peri-implant bone loss compared to normoglycemic mice after ligature-induced peri-implantitis. Based on the literature and our preliminary findings, the central hypothesis for this project is that 1) DM hyperglycemia induces peri-implant dysbiosis through aggravated systemic inflammation, and that 2) DM hyperglycemia-driven microbial changes promote peri-implant inflammation and bone loss. In this proposal, we will investigate the causality of oral microbial change under hyperglycemic condition and the effect of such change on peri-implant inflammation and bone loss in mice. In Aim 1, peri-implant and periodontal microbial changes under normal vs. DM conditions with or without intervention for inflammation and hyperglycemia will be identified and characterized by 16S rRNA sequencing and metagenomic analysis. Microbiota profiles in lesions of peri-implantitis and periodontitis in the same animal will be compared. Respective status of gingival inflammation and bone loss in the same animal will be determined and analyzed under each condition. In Aim 2, we will first use an in vitro culture system to examine the responses by oral mucosal epithelial cells and autogenous splenocytes to peri-implant microbiota from WT or diabetic mice with or without intervention for inflammation and hyperglycemia. Then, peri-implant microbiota from WT or diabetic mice will be transferred to WT recipient mice pre-treated with antibiotics, followed by the assessment of peri-implant inflammation and bone loss in vivo. For further mechanistic analysis, we will test the role of IL-17 and IFNg in hyperglycemia-associated peri-implant pathogenesis and characterize immune cell profile in peri-implant soft tissue microenvironment using single cell RNA sequencing (sc-RNAseq). Successful completion of this project will allow us to develop more comprehensive designs and translational approaches in the future to gain insight into peri-implantitis pathogenesis in DM patients.
Han, Xiaozhe, "Impact of Diabetes Hyperglycemia on Peri-Implantitis" (2023). NSU Grant Awards. 89.