Tooth Eruption: Role of Dental Follicle & PTH Receptor

牙齿萌出：牙囊的作用

• 批准号: 6581469
• 负责人: Laurie K. McCauley
• 金额: $ 28.91万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6581469
• 关键词: cell differentiation; dental development; developmental genetics; gel mobility shift assay; gene expression; genetic transcription; genetically modified animals; hormone receptor; hormone regulation /control mechanism; in situ hybridization; laboratory mouse; normal ossification; northern blottings; osteoclasts; parathyroid hormone related protein; parathyroid hormones; phenotype; tissue /cell culture; tooth; western blottings

DESCRIPTION (provided by applicant): The process of tooth eruption is dependent on numerous events, cells and factors, many of which have been initially identified, but are as of yet poorly defined. Existing evidence suggests that factors secreted by cells within the dental follicle region promote both the recruitment of mononuclear cells, and their differentiation into osteoclasts with subsequent alveolar bone resorption as required for tooth eruption. Paralleling tooth eruption is the development of a functional periodontal ligament (PDL). Maintenance of this non-mineralized ligament and post-functional eruption is also thought to be dependent on factors secreted by cells within the follicle/PDL region. Preliminary data indicate that dental follicle cells have receptors for parathyroid hormone-related protein (PTHrP) and observations that PTHrP knock-out mice have defective tooth eruption lead to the hypothesis that follicle cells are required for tooth eruption via their PTHrP-mediated stimulation of osteoclastic activity and inhibition of mineralization. Three specific aims will test this hypothesis using in vitro and in vivo models. The first will define the actions of PTHrP at the PTH type 1 receptor (PTH-1R) on cells in the microenvironment of the developing tooth that are considered to promote osteoclast differentiation and activation. The second aim will define the actions of PTHrP at the PTH-1 receptor on cells in the microenvironment of the developing tooth that are considered to inhibit mineralization and thus maintain a functional PDL and prevent ankylosis. Lastly, the third aim will identify and characterize the transcriptional mediators of osteoclast activators and mineralization inhibitors operative in facilitating tooth eruption. By identifying the mediators and signaling molecules of PTHrP during tooth eruption, these studies will provide critical information required for defining the molecular mechanisms operative during tooth eruption. This valuable information will facilitate the design of therapeutic and preventive strategies to address conditions of altered tooth development and eruption that contribute to malocclusion and compromised oral health and function. Furthermore, these studies will enhance our basic knowledge as to the role of PTHrP and PTH-1R interactions in controlling mineralized tissue homeostasis.

描述（由申请人提供）：牙齿萌出的过程取决于许多事件、细胞和因素，其中许多已被初步确定，但尚未明确定义。现有证据表明，牙滤泡区域内的细胞分泌的因子促进了单个核细胞的募集，并促进了它们向破骨细胞的分化，随后的牙槽骨吸收是牙齿萌出所必需的。平行出牙是一个功能牙周韧带（PDL）的发展。这种非矿化韧带的维持和功能性爆发也被认为依赖于卵泡/PDL区域内细胞分泌的因子。初步数据表明，牙滤泡细胞具有甲状旁腺激素相关蛋白（PTHrP）的受体，并且观察到PTHrP敲除的小鼠有缺陷的出牙，这导致了一种假设，即通过PTHrP介导的破骨细胞活性的刺激和矿化的抑制，出牙需要滤泡细胞。三个具体的目标将测试这一假设使用