The Role of microRNAs in Tooth Regeneration using the Mouse Incisor Model

使用小鼠门牙模型研究 microRNA 在牙齿再生中的作用

• 批准号: 7742472
• 负责人: Ophir D Klein
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7742472
• 关键词: Adult; Ameloblasts; Animals; Apoptosis; Area; Biological Assay; Biological Models; Biological Process; Biomedical Engineering; Cell Proliferation; Cells; Cellular Morphology; Data; Dental; Dental Enamel; Dental caries; Epithelial; Exploratory/Developmental Grant; Functional RNA; Gene Expression; Gene Expression Regulation; Generations; Genetic; Growth; Histologic; Incisor; Knowledge; Learning; Life; Messenger RNA; MicroRNAs; Modeling; Molecular; Mus; Natural regeneration; Nature; Nucleotides; Oligonucleotides; Oral cavity; Organ; Pathway interactions; Pattern; Play; Process; Public Health; Publishing; RNA Interference; Regulation; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Role; Signal Pathway; Signal Transduction; Small RNA; Stem cells; Syndrome; System; Tail; Testing; Therapeutic; Tissues; Tooth Loss; Tooth structure; Veins; adult stem cell; base; cell type; craniofacial; in vivo; interest; public health relevance; repaired; research study; self-renewal; sensor; stem; theories

DESCRIPTION (provided by applicant): Tooth bioengineering is of great interest, because dental decay and tooth loss constitute an important public health issue. Additionally, tooth anomalies are common in many craniofacial syndromes, and the easy accessibility of the oral cavity makes teeth an excellent test case for organ replacement. A thorough understanding of the molecular processes that drive tooth formation will be crucial to efforts to build new teeth. We are using the mouse incisor as a model for understanding the mechanisms that underlie the ability of stem cells to contribute to renewal of dental tissues, because it grows continuously due to the presence of adult stem cells. In this application we propose to learn about the natural role of RNAi in regulation of stem cell-driven tooth renewal by focusing on how endogenous small RNAi molecules called microRNAs (miRNAs) control continuous growth of the incisor. We will determine the spatial expression pattern of miRNAs in incisor stem cells and their progeny, ascertain the effects of miRNA knockdown on self-renewal and differentiation in cultured incisor stem cells, and determine the effects of in vivo miRNA knockdown on incisor continuous growth. Together, these experiments will open a portal into a previously unexplored area: the endogenous, natural role of RNAi in stem cell-based tooth regeneration. The knowledge we gain will inform therapeutic approaches that aim to manipulate molecular pathways in order to enhance tooth repair or regeneration. PUBLIC HEALTH RELEVANCE: Tooth bioengineering is of great interest, because dental decay and tooth loss constitute an important public health issue. A thorough understanding of the molecular processes that drive tooth formation will be crucial to efforts to build new teeth. We propose to learn about the natural role of RNA interference (RNAi) in regulation of stem cell-driven tooth renewal by focusing on how endogenous small RNAi molecules called microRNAs regulate this process.

描述（由申请人提供）：牙齿生物工程引起了人们极大的兴趣，因为蛀牙和牙齿脱落构成了一个重要的公共卫生问题。此外，牙齿异常在许多颅面综合征中很常见，口腔的易接近性使牙齿成为器官替代的绝佳测试案例。彻底了解驱动牙齿形成的分子过程对于构建新牙齿至关重要。我们使用小鼠门牙作为模型来了解干细胞促进牙组织更新能力的机制，因为它由于成体干细胞的存在而持续生长。在此应用中，我们建议通过关注称为 microRNA (miRNA) 的内源性小 RNAi 分子如何控制门牙的持续生长来了解 RNAi 在调节干细胞驱动的牙齿更新中的自然作用。我们将确定门牙干细胞及其后代中miRNA的空间表达模式，确定miRNA敲低对培养的门牙干细胞自我更新和分化的影响，并确定体内miRNA敲低对门牙持续生长的影响。总之，这些实验将为以前未探索的领域打开一扇大门：RNAi 在基于干细胞的牙齿再生中的内源性、自然作用。我们获得的知识将为旨在操纵分子途径以增强牙齿修复或再生的治疗方法提供信息。 公共健康相关性：牙齿生物工程引起了极大的兴趣，因为蛀牙和牙齿脱落构成了重要的公共健康问题。彻底了解驱动牙齿形成的分子过程对于构建新牙齿至关重要。我们建议通过关注称为 microRNA 的内源性小 RNAi 分子如何调节这一过程来了解 RNA 干扰 (RNAi) 在调节干细胞驱动的牙齿更新中的自然作用。