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.

项目摘要（家长奖） 由于美观性差和牙齿缺失，外伤或疾病造成的牙齿缺失仍然是全世界关注的一个重大问题。 功能。解决这个问题并非易事，因为牙槽骨和口腔组织的再生并非易事。 可以预见，部分原因是过程的复杂性。这些缺陷的骨再生仍然存在 不可预测并了解指导骨髓生物学的生理机制 炎症消退将提高未来这些再生技术的治疗可靠性。 我们观察到生长停滞特异性 6 (GAS6) 在控制牙槽骨方面发挥着以前未知的作用 以及拔牙后的软组织再生。 GAS6缺陷小鼠的愈合能力明显较差 拔牙后，这与异常的骨和免疫表型有关。主要目标为 该提案旨在测试 GAS6 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 GAS6 信号传导影响间充质细胞的启动 干细胞朝向成骨细胞谱系。这个假设将通过愈合测量来检验 在提取缺乏 GAS6 信号传导的小鼠间充质干细胞后，以及相关的 对提取后来自患者的原代细胞进行实验。我们还假设增加 GAS6 缺乏时的中性粒细胞浸润会阻碍牙槽骨再生。我们将聘用模特 中性粒细胞和中性粒细胞功能的条件敲除模型来检验这一假设。该奖项将 为理解口腔愈合的生理学做出了重大贡献，同时 最终为候选人提供使用遗传小鼠模型和免疫学的重要培训 成为一名专门从事系统治疗的牙科临床医生科学家的独立职业 受损的患者。