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.

项目概要根尖周炎 (AP) 是一种非常普遍且使人衰弱的病理状况，其特点是牙齿感染引起的骨吸收和疼痛。许多优雅的研究揭示了 AP 中免疫细胞和炎症介质的功能。尽管AP密集由三叉神经节 (TG) 纤维支配，这些传入神经参与这种疾病过程很大程度上是未知的。我们的初步数据表明 TG 神经元调节 AP 病变发展。本提案的目的是了解 TG 光纤如何控制 AP 发展，这方面仍然存在很大的知识差距。我们第一次提议研究四种神经元/非神经元细胞相互作用在控制 AP 发展中的作用 TG 神经元的主要亚类。这是一种新颖且至关重要的策略感觉神经元对 AP 发育调节的研究，因为每个神经元亚类具有独特的功能和生化组成，包括独特的受体组、离子通道和神经肽。因此，TG 神经元亚群的调节潜力可能变化很大；甚至对破骨细胞和成骨细胞产生相反的作用。所以根据文献和初步实验，我们设计了一种新的AP学习策略 TG 神经元的发育。我们的中心假设是，为了应对感染，某些 TG 传入神经的亚类通过调节破骨细胞和成骨细胞活性。该假设将在以下方面进行检验：目标 1 检查角色不同亚类TG传入抑制骨吸收和免疫学研究感染诱导的 AP 小鼠模型中的反应；目标 2 定义不同群体的参与 TG 神经元亚类对破骨细胞和成骨细胞功能的调节；和目标 3 定义和识别 TG 神经元不同亚类释放的可溶性因子及其对破骨细胞和成骨细胞功能调节的贡献。我们相信该应用程序生成的知识将对双方产生重大的积极影响科学和临床的观点。从科学上讲，这是主要的新颖方法使用亚类特异性 TG 小鼠品系研究 AP。此外，生成的新深入了解神经元和 DCS 重塑之间的相互作用将为进一步研究开辟途径科学进步。在临床上，神经元调节机制的识别可以提供新的策略，重要的是，开发抗 AP 疗法的目标。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Trigeminal neurons control immune-bone cell interaction and metabolism in apical periodontitis.

三叉神经元控制根尖周炎中的免疫-骨细胞相互作用和代谢。

DOI：
发表时间：
2022-05-31
期刊：
影响因子：
0
作者：
Austah, Obadah N;Lillis, Katherine V;Akopian, Armen N;Harris, Stephen E;Grinceviciute, Ruta;Diogenes, Anibal
通讯作者：
Diogenes, Anibal

Intraretinal Layer Segmentation Using Cascaded Compressed U-Nets.

使用级联压缩 U-Net 进行视网膜内层分割。

DOI：
发表时间：
2022-05-17
期刊：
影响因子：
0
作者：
Yadav, Sunil Kumar;Kafieh, Rahele;Zimmermann, Hanna Gwendolyn;Kauer;Nouri;Mohammadzadeh, Vahid;Shi, Lynn;Kadas, Ella Maria;Paul, Friedemann;Motamedi, Seyedamirhosein;Brandt, Alexander Ulrich
通讯作者：
Brandt, Alexander Ulrich

Risk factors for microcystic macular oedema in glaucoma.

青光眼黄斑微囊水肿的危险因素。

DOI：
发表时间：
2023-04
期刊：
影响因子：
0
作者：
Mahmoudinezhad, Golnoush;Salazar, Diana;Morales, Esteban;Tran, Peter;Lee, Janet;Hubschman, Jean;Nouri;Caprioli, Joseph
通讯作者：
Caprioli, Joseph

Comparing Rates of Change in Moderate to Advanced Glaucoma: Retinal Nerve Fiber Layer Versus Bruch Membrane Opening-Minimum Rim Width.

比较中度至晚期青光眼的变化率：视网膜神经纤维层与布鲁赫膜开口 - 最小边缘宽度。