The Role of microRNA-21, 27 and 29 in Tooth Movement

microRNA-21、27 和 29 在牙齿移动中的作用

• 批准号: 8967993
• 负责人: Phimon Atsawasuwan
• 金额: $ 13.95万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8967993
• 关键词: 3-Dimensional; Advisory Committees; Affect; Animal Genetics; Area; Basic Science; Biological; Biological Assay; Biology; Biopharmaceutics; Bone Density; Bone Resorption; Bone remodeling; CDC42 gene; Caring; Cell Culture Techniques; Cell Differentiation process; Cell physiology; Cells; Chicago; Clinical; Complex; Coupled; Dental caries; Dentistry; Deposition; Development; Dicer Enzyme; Down-Regulation; Ensure; Epigenetic Process; Event; Exhibits; Extracellular Matrix; Family; Fibroblasts; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Gingivitis; Goals; Homeostasis; Human; Illinois; In Situ Hybridization; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Maps; Mechanics; Mentors; Mentorship; Michigan; MicroRNAs; Modality; Modeling; Mus; National Institute of Dental and Craniofacial Research; Oral health; Orthodontic; Osteoblasts; Osteoclasts; Patients; Pattern; Pennsylvania; Periodontal Ligament; Periodontic specialty; Periodontium; Play; Principal Investigator; Procedures; Process; Rattus; Regulation; Reporting; Research; Research Activity; Research Personnel; Research Project Grants; Research Training; Reverse Transcriptase Polymerase Chain Reaction; Role; Root Resorption; Rotation; Scientific Advances and Accomplishments; Scientist; Side; Stretching; TRANCE protein; Techniques; Testing; Texas; Time; Tissues; Tooth Movement; Training; Translational Research; Universities; Up-Regulation; alveolar bone; base; bone; cell type; cohort; college; compliance behavior; craniofacial; design; drug development; experience; high risk; human DICER1 protein; improved; inhibitor/antagonist; insight; mouse model; nanoscale; novel; osteoclastogenesis; overexpression; particle; public health relevance; response; skills

 DESCRIPTION (provided by candidate): The Mentored Clinical Scientist Research Career Development Award (K08) from NIDCR will provide the principal investigator who is an orthodontist with his background of periodontics and basic science training with the opportunity to receive additional scientific knowledge and research training in microRNA biology, epigenetics and drug development and protected time for his research activities. Recently emerging evidences show that microRNAs play a significant role in the development and remodeling of tissues through the regulation of large sets of extracellular matrix (ECM) genes. Orthodontic tooth movement is a complex biological event that involves the coordinated expression regulation of large sets of ECM genes, including a set of bone resorption effectors on the compression side and a set of matrix anabolic genes on the tension side. The principal investigator has demonstrated that microRNAs play important roles in tooth movement in a mouse model and different modes of forces induce different expression patterns of microRNA-21, 27 and29 as well as their target genes in cell cultures and a rat model. The hypothesis of this proposed research is that microRNA-21, 27 and 29 expression in periodontal tissues affects tooth movement by altering ECM gene expression levels, resulting in increased anabolic activity of ECM genes and new matrix deposition on the tension side in tandem with osteoclastogenesis and decreased bone mineral density on the compression side. The specific aims of this proposed research are 1) To determine and compare the effect of miR-21, 27 and 29 modulation on key periodontal cell types, periodontal ligament fibroblasts, osteoblasts, and osteoclasts, in 2- and 3-dimensional cell cultures and in response to mechanical loading; 2) To map the spatial and temporal expression of miR-21, 27 and 29 family expression during orthodontic tooth movement; 3) To determine the ability of miR-21, 27 and 29 mimics and inhibitors to affect the rate of tooth movement in a rat model. This career development award will involve didactic courses, laboratory rotations, a research project, and the guidance and expertise of world-class investigators. Under the mentorship of Drs. Salvador Nares and Thomas Diekwisch, and the experience and insights of a diverse Advisory Committee from the areas of microRNA biology, epigenetics, animal genetics and biopharmaceutics, the Career Development Award will ensure that the principal investigator can continue his professional development and achieve his goal of becoming an independent investigator. The training will be held mainly at the University of Illinois at Chicago (UIC) College of Dentistry with a number of laboratory rotation sessions at the Texas A&M University, the University of Pennsylvania and the University of Michigan at Ann Arbor for the principal investigator to gain his skills in the techniques and advice required in the research application. The ultimate goal of the proposed research is to improve orthodontic care by contributing to translational research and leading to the development of a novel microRNA-based approach as the principal investigator develops to be an independent orthodontist/ researcher.

 描述（由候选人提供）：NIDCR 的指导临床科学家研究职业发展奖 (K08) 将为具有牙周病学和基础科学培训背景的正牙医生的首席研究员提供接受 microRNA 生物学、表观遗传学和药物开发方面额外科学知识和研究培训的机会，并为其研究活动提供受保护的时间。最近出现的证据表明，microRNA 通过调节大量细胞外基质 (ECM) 基因，在组织的发育和重塑中发挥着重要作用。正畸牙齿移动是一个复杂的生物事件，涉及大量 ECM 基因的协调表达调节，包括一组压缩侧的骨吸收效应器和一组张力侧的基质合成代谢基因。主要研究人员证明，microRNA 在小鼠模型中的牙齿移动中发挥着重要作用，不同的力模式会诱导细胞培养物和大鼠模型中 microRNA-21、27 和 29 及其靶基因的不同表达模式。这项研究的假设是，牙周组织中的 microRNA-21、27 和 29 表达通过改变 ECM 基因表达水平来影响牙齿移动，导致 ECM 基因的合成代谢活性增加，张力侧新基质沉积，同时破骨细胞生成，压缩侧骨矿物质密度降低。本研究的具体目的是 1) 确定并比较 2 维和 3 维细胞培养物中 miR-21、27 和 29 调节对关键牙周细胞类型、牙周膜成纤维细胞、成骨细胞和破骨细胞的影响以及对机械负荷的反应； 2）绘制正畸牙齿移动过程中miR-21、27和29家族表达的空间和时间表达图； 3) 确定miR-21、27和29模拟物和抑制剂影响大鼠模型中牙齿移动速率的能力。该职业发展奖将涉及教学课程、实验室轮换、研究项目以及世界级研究人员的指导和专业知识。在博士的指导下。 Salvador Nares 和 Thomas Diekwisch 以及来自 microRNA 生物学、表观遗传学、动物遗传学和生物制药领域的多元化咨询委员会的经验和见解，职业发展奖将确保主要研究者能够继续其专业发展并实现成为独立研究者的目标。培训将主要在伊利诺伊大学芝加哥分校 (UIC) 牙科学院举行，并在德克萨斯农工大学、宾夕法尼亚大学和密歇根大学安娜堡分校进行一些实验室轮换课程，以便首席研究员获得研究应用所需的技术和建议方面的技能。拟议研究的最终目标是随着主要研究者发展成为一名独立的正畸医生/研究员，通过促进转化研究并导致开发基于 microRNA 的新型方法来改善正畸护理。