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Trigeminal Afferents Regulation of Apical Periodontitis Development

三叉神经传入对根尖牙周炎发展的调节

基本信息

批准号：
10454305
负责人：
Anibal Diogenes
金额：
$ 35.86万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10454305
关键词：
Ablation Address Affect Afferent Neurons Alkaline Phosphatase Amyloid beta-Protein Biochemical Biological Biological Assay Bone Pain Bone Resorption Bone remodeling C Fiber Capsaicin Cell Communication Cell Line Cells Chemicals Clinical Coculture Techniques Data Dental Development Disease Fiber Flow Cytometry Genetic Goals High Pressure Liquid Chromatography Human Immune response Immunohistochemistry Infection Inflammation Mediators Investigation Ion Channel Knowledge Lesion Life Lipids Literature Measures Mediating Microcomputers Microscopy Minerals Mus Neuroglia Neurons Neuropeptides Nociceptors Osteoblasts Osteoclasts PF4 Gene Pain Pathogenesis Pathologic Pathologic Processes Pathway interactions Patients Periapical Periodontitis Pharmaceutical Preparations Process Protein Array Proteins Proteomics Quality of life Quantitative Reverse Transcriptase PCR Receptor Signaling Regulation Research Role Sensory Signal Pathway Skeletal system Spectrophotometry Stains Structure Structure of trigeminal ganglion Testing Therapeutic Time Tissues Tooth Loss Transgenic Mice Trigeminal System United States attenuation base bone loss clinically significant craniofacial density dental infection design experimental study gel electrophoresis global health immune function immunoreactivity in silico in vivo innovation insight lipidomics mouse model nerve supply novel novel strategies novel therapeutics oral condition osteoblast differentiation precursor cell premature receptor release factor response screening targeted treatment tomography

项目摘要

Project Summary Apical periodontitis (AP) is a highly prevalent and debilitating pathological condition marked by bone resorption and pain as result of dental infections. Many elegant studies have revealed the functions of immune cells and inflammatory mediators in AP. Despite AP being densely innervated by trigeminal ganglia (TG) fibers, the participation of these afferents in this disease process is largely unknown. Our preliminary data demonstrate that TG neurons regulate AP lesion development. The objective of this proposal is to understand how TG fibers control AP development, which remains a large gap in knowledge. We, for the first time, propose to investigate neurons/non-neuronal cell interaction in control of AP development for each of four major subclasses of TG neurons. This is novel and critically important strategy in approaching research on regulation of AP development by sensory neurons, since each neuronal sub-class has distinct function and biochemical make up, including unique sets of receptors, ion channels and neuropeptides. Hence, it is possible that regulatory potential of TG neuronal subsets could dramatically vary; and even produce opposite effects on osteoclasts and osteoblasts. So according to literature and preliminary experiments, we designed a novel strategy on study AP development by TG neurons. Our central hypothesis is that in response to infection certain subclasses of TG afferents inhibit bone resorption in apical periodontitis via the regulation of osteoclastic and osteoblastic activities. This hypothesis will be tested in: Aim 1 examining role of different subclasses of TG afferents in inhibiting bone resorption and immunological responses in a murine model of infection-induced AP; Aim 2 defining involvement of different subclasses of TG neurons on regulation of osteoclastic and osteoblastic functions; and Aim 3 defining and identifying the released soluble factor(s) from different subclasses of TG neurons and their contribution to modulation of osteoclast and osteoblast functions. We believe that knowledge generated by this application will have a substantial positive impact from both scientific and clinical perspectives. Scientifically, this is the principally novel approach in investigation of AP using subclass-specific TG mouse lines. Moreover, the generated new insight into interactions between neurons and DCS remodeling will open pathways for further scientific advancement. Clinically, identification of neuronal regulatory mechanisms could offer novel strategies and, importantly, targets for developing anti-AP therapeutics.

项目总结