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.

项目简介（家长奖）