Impact of Diabetes hyperglycemia on peri-implantitis

抽象的。 在种植体植入后的10年内，大约30%的患者会患上种植体周围炎。 以软组织感染、炎症和种植体周围的骨吸收为特征。关联的 社会经济负担很大，患者经常出现慢性和令人痛苦的症状。 最近的研究表明糖尿病(DM)高血糖是种植体周围炎的危险因素。然而， 目前尚不清楚高血糖是如何导致种植体周围炎的。没有明确的认识 对其发生机制及相应的干预措施的研究表明，糖尿病患者大量接受种植牙 植入物将继续面临发生种植体周围炎的潜在更高风险。我们的初步数据 使用实验性种植体周围炎的小鼠模型证明不同的口腔微生物组成 在高血糖小鼠和正常血糖小鼠之间观察到，高血糖小鼠表现出上调 与正常血糖相比，促炎症细胞因子(IL-17和干扰素)和种植体周围骨丢失更大 小鼠结扎后种植体周围炎。根据文献和我们的初步调查结果，中央 该项目的假设是：1)糖尿病高血糖通过加重导致种植体周围生生物失调 全身性炎症，以及2)糖尿病高血糖引起的微生物变化促进种植体周围期 发炎和骨质流失。在这项建议中，我们将调查口腔微生物变化的因果关系 高血糖状态及其对小鼠种植体周围炎症和骨丢失的影响。在……里面 目标1：种植体周和牙周微生物在正常和DM条件下的变化 将通过16S rRNA测序来识别和表征对炎症和高血糖的干预 和元基因组分析。同一动物种植体周围炎和牙周炎病变的微生物区系特征 将会被比较。将确定同一动物的牙周炎和骨质丢失的各自状态 并对每种情况下的情况进行了分析。在目标2中，我们将首先使用体外培养系统来检查反应。 口腔黏膜上皮细胞和自体脾细胞植入WT或糖尿病小鼠种植周微生物区系 对炎症和高血糖进行干预或不干预。然后，来自WT或WT的种植体周围微生物群 将糖尿病小鼠转移到经抗生素预处理的WT受体小鼠，随后评估 种植体周围炎症和体内骨丢失。为了进一步的机制分析，我们将测试IL-17的作用 和干扰素在种植体周围高血糖相关发病机制中的作用及周围免疫细胞特性的研究 植入软组织微环境的单细胞RNA测序(sc-RNAseq)。成功完成 该项目将允许我们在未来开发更全面的设计和翻译方法，以 深入了解糖尿病患者种植体周围炎的发病机制。

Abstract. 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 IFN) 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 IFN 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.