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PPARs and periodontal disease

PPAR 和牙周病

基本信息

批准号：
9309421
负责人：
FRANK C GIBSON
金额：
$ 17.28万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9309421
关键词：
Agonist Animal Model Area Bacterial Infections Cell Line Cell model Cells Chronic Clinical Research Clinical Treatment Complement Receptor Complex Coupled Data Debridement Development Elements Epithelial Cells Forsythia Future Gene Expression Gingiva Health Human Human Cell Line Immune Immune response Immunoglobulin G In Vitro Infection Inflammation Inflammatory Inflammatory Response Investigation Knowledge Ligature Measurement Measures Modality Modeling Mus Nuclear Hormone Receptors Operative Surgical Procedures Oral Outcome PPAR alpha PPAR gamma PPAR-beta Pathogenesis Pathology Patients Periodontal Diseases Peroxisome Proliferator-Activated Receptors Play Porphyromonas gingivalis Production Publishing Receptor Gene Recovery Role TNF gene Testing Therapeutic Therapeutic Uses Tissues Treponema denticola antimicrobial base bone loss cytokine human tissue in vivo Model macrophage mouse model new therapeutic target novel novel strategies oral infection pathogen prevent response scaling and root planing targeted treatment therapeutic target translational study treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Porphyromonas gingivalis (Pg) is a keystone periodontal pathogen. Controlling chronic inflammation elicited by periodontal pathogens is thought central to mitigating soft and hard tissue destruction that characterizes periodontal disease (PD). Clinical treatment of patients with moderate to severe PD typically requires highly invasive approaches. Thus, development of non-invasive measures to therapeutically regulate pathogen-driven inflammation and limit oral bone loss are sought to augment current PD clinical treatment modalities. Recent studies have identified that one group of nuclear hormone receptors, peroxisome proliferator-activated receptors (PPARs), as potential molecules of therapeutic value as PPARs have been shown to control expression of genes involved in inflammation. Although some supportive data exists regarding the role played by PPARs in pathogen- induced inflammation, there is a significant gap in our knowledge in the context of PD-associated bacterial infection-elicited inflammation, and oral bone loss. Based on our preliminary data, and the gap in knowledge regarding specific PPAR exploitation as a therapeutic target for controlling Pg infection-elicited inflammation and oral bone loss, we propose that that PPARs control the expression of key inflammatory elements that contribute inflammation and oral bone loss elicited by the defined periodontal pathogen Pg. Our approach, will utilize an in vitro screen employing human tissue resident macrophages and epithelial cells to identify a PPAR agonist or antagonist that most significantly reduces cellular inflammatory response to Pg challenge. This PPAR-targeting molecule will then be tested in an animal model to define its therapeutic value in reducing Pg oral infection- elicited inflammation and oral bone loss.

描述（由申请人提供）：牙龈卟啉单胞菌（Pg）是一种重要的牙周病原体。控制由牙周病原体引起的慢性炎症被认为是减轻牙周病（PD）特征的软组织和硬组织破坏的核心。中重度PD患者的临床治疗通常需要高侵入性方法。因此，寻求开发治疗性调节病原体驱动的炎症和限制口腔骨丢失的非侵入性措施来增强当前的PD临床治疗模式。最近的研究已经确定，一组核激素受体，过氧化物酶体增殖物激活受体（PPARs），作为具有治疗价值的潜在分子，PPARs已经显示出控制参与炎症的基因的表达。尽管存在一些关于PPARs在病原体诱导的炎症中所起作用的支持性数据，但我们在PD相关细菌感染引起的炎症和口腔骨丢失方面的知识存在显著差距。基于我们的初步数据，以及关于特定的PPAR开发作为控制Pg感染引起的炎症和口腔骨丢失的治疗靶点的知识上的差距，我们提出PPARs控制关键炎症元件的表达，这些炎症元件促成由定义的牙周病原体Pg引起的炎症和口腔骨丢失。我们的方法，将利用体外筛选，采用人体组织驻留的巨噬细胞和上皮细胞来鉴定最显著地降低对Pg激发的细胞炎症反应的PPAR激动剂或拮抗剂。然后将在动物模型中测试这种PPAR靶向分子，以确定其在减少Pg口腔感染引起的炎症和口腔骨丢失中的治疗价值。