IInfection-Elicited Oral Bone Loss: TLR2, Ontogency, and Porphromonas Gingivalis

感染引起的口腔骨丢失：TLR2、个体发育和牙龈卟啉单胞菌

基本信息

批准号：
7579128
负责人：
FRANK C GIBSON
金额：
$ 31.85万
依托单位：
BOSTON MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7579128
关键词：
Adult Age Age-Months Alveolar Bone Loss Animals Bacteria Binding CD14 gene Cell Adhesion Molecules Chronic Communicable Diseases Detection Disease Disease susceptibility Epidemiologic Studies Genes Genetic Polymorphism Growth Human Immune response Immune system Immunologic Receptors In Vitro Incidence Individual Infection Inflammation Inflammatory Inflammatory Response Interferon-beta Interleukin-6 Knock-out Knowledge Life Measurable Mediating Modeling Mus Myelogenous Oral Oral cavity Organism Pattern Periodontal Diseases Periodontitis Play Porphyromonas gingivalis Production Proteins Receptor Signaling Regulation Relative (related person)Research Personnel Role Signal Pathway Signal Transduction Signaling Molecule Site Staging Structure of gingival sulcus TLR2 gene TLR4 gene Toll-like receptors United States age related base bone loss chemokine cytokine defined contribution fimbria in vivo macrophage microbial mouse model osteoclastogenesis pathogen programs receptor receptor-mediated signaling research study response toll-like receptor 4

项目摘要

DESCRIPTION (provided by applicant): Periodontal disease is one of the most common chronic infectious diseases of humans and it has been estimated that in the United States alone 100,000,000 people possess measurable periodontal bone loss. Importantly, periodontal disease is increasingly more common in adults as they age suggesting that ontogeny impacts periodontal disease susceptibility and / or inflammatory progression. A myriad of bacteria inhabit the oral cavity; however, Porphyromonas gingivalis has been identified as a primary etiological agent associated with human periodontal disease. Based on two epidemiological studies, the toll-like receptors (TLRs; a group of innate immune receptors that recognize distinct microbial patterns) have been implicated in progression of human periodontal disease. However, to date, experimental studies have not been performed to directly assess the role for TLRs, or the adaptor molecules involved in TLR-mediated signaling in oral bone loss in the context of a specific periodontal disease pathogen. Moreover, there is a lack of knowledge regarding modeling long-term patterns of oral bone loss in response to infection. In this study, we propose 1- To define the role of TLR2 and TLR4 in the age-related innate immune response to P. gingivalis and fimbriae; 2- To define the role of MyD88-dependent and MyD88-independent signaling in the age-related innate immune response to P. gingivalis and fimbriae; and 3- To define the roles for the TLR2 and TLR4 receptors and MyD88-dependent and MyD88-independent signaling cascades in age-related oral bone loss patterns in mice in response to P. gingivalis infection. These studies will: 1- elucidate the contribution of ontogeny to the host inflammatory response to P. gingivalis in vitro; 2- define the age-related progression of oral bone loss in a murine model in response to P. gingivalis infection; and 3- and assess the contribution of TLR2 and TLR4, as well as TLR adaptor molecules including MyD88 in this response. These studies provide for a thorough examination of the mechanisms underlying the role played by specific TLR receptors to P. gingivalis-elicited inflammation and oral bone loss in the context of age.

描述（由申请人提供）：牙周疾病是人类最常见的慢性传染病之一，据估计，仅在美国，就有1亿人拥有可衡量的牙周骨质流失。重要的是，随着年龄的增长，牙周疾病在成年人中越来越普遍，这表明个体发育会影响牙周疾病的易感性和 /或炎症进展。无数细菌居住在口腔中；然而，卟啉症已被确定为与人牙周疾病相关的主要病因。基于两项流行病学研究，Toll样受体（TLR；一组识别不同微生物模式的先天免疫受体）与人类牙周疾病的进展有关。然而，迄今为止，尚未进行实验研究直接评估TLR的作用，或者在特定牙周疾病病原体的背景下，在口腔骨质流失中涉及TLR介导的信号传导的衔接子分子。此外，缺乏关于响应感染的长期口腔丢失的长期模式的知识。在这项研究中，我们提出1-来定义TLR2和TLR4在与年龄相关的先天免疫反应中对牙龈疟原虫和fimbriae的作用； 2-定义了MyD88依赖性和MyD88独立的信号在与年龄相关的先天免疫反应中对牙龈疟原虫和fimbriae的作用； 3-以定义TLR2和TLR4受体的作用以及MyD88依赖性和MYD88独立的信号传导在年龄相关的口腔骨损失模式中，响应于牙龈疟原虫感染。这些研究将：1-在体外阐明个体对宿主炎症反应的贡献； 2-定义响应牙龈疟原虫感染的鼠模型中与年龄相关的口腔骨骼流失的进展； 3-并评估TLR2和TLR4的贡献，以及在此响应中包括MyD88在内的TLR适配器分子。这些研究提供了对特定TLR受体在年龄范围内特异性TLR受体起作用的作用的机制。