GAS6-mediated alveolar bone regeneration - Admin Supplement

项目总结(家长奖) 创伤或疾病导致的牙齿脱落仍然是一个重要的世界性问题，因为缺乏美感和牙齿缺失 功能。解决这个问题不是一件容易的事，因为牙槽骨和口腔组织的再生不是 这是可以预测的，部分原因是这一过程的复杂性。这些缺损处的骨再生仍然存在 不可预测和了解指导骨髓生物学和 炎症消解将增加这些再生技术在未来的治疗可靠性。 我们观察到以前未知的生长抑制特异体6(Gas6)在控制牙槽骨中的作用。 拔除后软组织再生。Gas6基因缺陷小鼠的愈合明显较差 拔牙后，这与异常的骨骼和免疫表型有关。的主要目标是 这项建议是为了测试Gas6在牙槽骨愈合中的关键作用。提出了两个具体目标 基于我们之前的观察。我们假设Gas6信号影响间充质细胞的启动 干细胞向成骨细胞方向发展。这一假设将通过愈合的测量来检验。 在Gas6信号缺陷的间充质干细胞小鼠中提取后， 对摘除后患者的原代细胞进行实验。我们还假设增加了 中性粒细胞在Gas6缺陷中的渗透阻碍了牙槽骨的再生。我们将雇佣模特 中性粒细胞和中性粒细胞功能的条件性基因敲除模型来验证这一假设。这一奖项将 为理解口腔愈合的生理学提供了重要的帮助 为应聘者提供使用遗传小鼠模型和免疫学的重要培训，最终 成为一名独立的牙科临床医生--专门从事系统治疗的科学家 有危险的病人。

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.