GAS6-mediated alveolar bone regeneration - Admin Supplement

GAS6 介导的牙槽骨再生 - 管理补充

• 批准号: 10871172
• 负责人: Ann Marie Decker
• 金额: $ 10.92万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10871172
• 关键词: Address; Affect; Award; Biology; Bone Marrow; Bone Regeneration; Bone Tissue; Cells; Defect; Dental; Disease; Esthetics; Future; Genetic; Goals; Growth; Immune; Immunology; Inflammatory; Measurement; Mediating; Mesenchymal Stem Cells; Modeling; Mus; Natural regeneration; Neutrophil Infiltration; Oral; Oral cavity; Parents; Pathway interactions; Patients; Phenotype; Physiological; Physiology; Process; Resolution; Role; Scientist; Signal Transduction; Testing; Therapeutic; Tooth Loss; Training; Trauma; alveolar bone; bone; bone healing; career; conditional knockout; experimental study; healing; loss of function; mouse model; neutrophil; oral tissue; regenerative approach; soft tissue; tissue regeneration

PROJECT SUMMARY (Parent Award) Tooth loss from trauma or disease remains a significant world-wide concern due to poor esthetics and loss of function. Addressing this issue is not trivial because regeneration of alveolar bone and oral tissue is not predictable, partially due to the complexity of the process. Bone regeneration of these defects remains unpredictable and understanding the physiological mechanisms that guide bone marrow biology and inflammatory resolution will increase the therapeutic reliability of these regenerative techniques in the future. We have observed a previously unknown role for Growth Arrest Specific 6 (GAS6) in controlling alveolar bone and soft tissue regeneration following extraction. GAS6-deficient mice showed markedly worse healing following extraction, which was associated with aberrant bone and immune phenotypes. The primary goal for this proposal is to test the critical role of GAS6 in alveolar bone healing. Two specific aims are proposed based on our previous observations. We hypothesize that GAS6 signaling affects the priming of mesenchymal stem cells towards the osteoblastic lineage. This hypothesis will be tested through measurement of healing following extraction in mice with mesenchymal stem cells deficient in GAS6 signaling, along with associated experiments on primary cells derived from patients following extraction. We also hypothesize that increased neutrophil infiltrate in GAS6-deificiency impedes alveolar bone regeneration. We will employ models conditional knockout models of neutrophils and neutrophil functions to test this hypothesis. This award will provide a significant contribution to the understanding of the physiology of healing in the oral cavity while providing significant training to the candidate in the use of genetic mouse models and immunology, ultimately leading to an independent career as a dental clinician-scientist specializing in treatment of systemically compromised patients.

项目概要（家长奖） 由创伤或疾病引起的牙齿缺失仍然是一个重要的世界性问题，这是由于美学差和牙齿缺失。 功能解决这个问题并不简单，因为牙槽骨和口腔组织的再生并不容易。 这是可以预测的，部分原因是过程的复杂性。这些缺损的骨再生仍然存在 不可预测的和理解的生理机制，指导骨髓生物学， 炎症消退将在未来增加这些再生技术的治疗可靠性。 我们已经观察到生长抑制特异性6（GAS 6）在控制牙槽骨中的一个先前未知的作用 和软组织再生。GAS 6缺陷小鼠的愈合情况明显较差 提取后，这与异常的骨和免疫表型有关。的首要目标 本发明旨在检测GAS 6在牙槽骨愈合中的关键作用。提出了两个具体目标 根据我们之前的观察我们假设GAS 6信号传导影响间充质细胞的启动， 干细胞向成骨细胞谱系发展。这一假设将通过测量愈合进行检验 在用GAS 6信号传导缺陷的间充质干细胞提取小鼠后，沿着相关的 对提取后来源于患者的原代细胞进行的实验。我们还假设， GAS 6缺乏时中性粒细胞浸润阻碍牙槽骨再生。我们会雇佣模特 嗜中性粒细胞和嗜中性粒细胞功能的条件性敲除模型来检验这一假设。这个奖项将 为理解口腔愈合的生理学做出了重大贡献， 为候选人提供使用遗传小鼠模型和免疫学的重要培训， 从而成为一名独立的牙科临床医生-科学家，专门从事系统性 妥协的病人