MOLECULAR BASIS OF TOOTH ERUPTION

牙齿萌出的分子基础

• 批准号: 6379645
• 负责人: GARY E WISE
• 金额: $ 17.38万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 2003-04-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379645
• 关键词: RNase protection assay; biological signal transduction; colony stimulating factor; dental development; epidermal growth factor; gene expression; gene targeting; genetically modified animals; hormone regulation /control mechanism; immunocytochemistry; interleukin 1; interleukin 6; laboratory mouse; laboratory rat; molecular biology; monocyte chemoattractant protein 1; osteoclasts; parathyroid hormone related protein; physiologic bone resorption; polymerase chain reaction; protein structure function; protooncogene; tissue /cell culture

The dental follicle, a loose connective tissue sac which surrounds the tooth, is required for eruption, and along with the adjacent stellate reticulum (SR), contains genes coding for the probable eruption molecules. A cascade of molecular signals in which there is cross-talk between the follicle and SR may initiate the cellular events of eruption; namely, early postnatal recruitment of mononuclear cells to the follicle to form osteoclasts needed for bone resorption to form the eruption pathway. Thus, it is the objective of this proposal to determine if certain of these molecules present in vivo are required for eruption and what is the role of such molecules in initiating the cellular events. To that end, monocyte chemotactic protein-1 (MCP-1), a molecule present in the dental follicle, will be injected into rats to determine its effect on the time of eruption and its ability to recruit the mononuclear cells into the follicle. The ability of the follicle cells to secrete MCP-1 in response to other putative eruption molecules also will be determined. Two molecules present in the SR, interleukin-1alpha (IL-1alpha) and parathyroid hormone related protein (PTHrP), may signal molecules in the follicle to initiate eruption. Injections of these molecules, use of null mice devoid of the receptor gene for IL-1alpha, and analysis of gene expression by RT-PCR and ribonuclease protection assay techniques all will be used to determine if these molecules are necessary for eruption, as well as determining how they affect gene expression and mononuclear cell numbers. Gene expression and immunolocalization of interleukin-6 in the follicle also will be examined. By determining what local molecular signals are required for eruption, an understanding of why teeth sometimes do not erupt (e.g., third molars in humans) may be gained. In turn, molecular treatment may someday be used to induce impacted teeth to erupt, as well as perhaps initiate tooth movement that often is required in orthodontics. Additionally, because bone resorption is required for eruption, these studies also will provide answers about the molecular basis of alveolar bone resorption, an understanding of which is critical in treatment of periodontal diseases.

牙齿卵泡是一种散发牙齿的松散结缔组织囊，喷发需要牙齿，并与邻近的星状网状（SR）一起包含编码可能的喷发分子的基因。 一连串的分子信号，其中卵泡和SR之间存在串扰可能会引发喷发的细胞事件。也就是说，早期产后募集单核细胞向卵泡形成骨吸收所需的破骨细胞，以形成喷发途径。 因此，该提案的目的是确定喷发中存在的某些这些分子是否需要，以及此类分子在启动细胞事件中的作用是什么。 为此，将将存在的单核细胞趋化蛋白-1（MCP-1）注射到大鼠中，以确定其对喷发时间的影响及其将单核细胞募集到卵泡中的影响。 还将确定卵泡细胞分泌MCP-1以响应其他推定的喷发分子的能力。 SR中存在的两个分子，介体1阿尔法（IL-1Alpha）和甲状旁腺相关蛋白（PTHRP）可能会在卵泡中表明卵泡中的分子以启动喷发。对这些分子的注射，使用没有受体基因的无效小鼠在IL-1Alpha中的使用，以及通过RT-PCR和核糖核酸酶保护测定技术对基因表达进行分析，所有这些都将用于确定这些分子是否需要用于喷发，并确定它们如何影响基因表达和单核细胞数。 还将检查白介素6在卵泡中的基因表达和免疫定位。 通过确定喷发需要哪些局部分子信号，可以理解为什么有时不爆发牙齿（例如，人类中的第三磨牙）。 反过来，有一天可以使用分子治疗来诱导受影响的牙齿爆发，并可能启动正畸经常需要的牙齿运动。 此外，由于喷发需要骨吸收，这些研究还将提供有关肺泡骨吸收的分子基础的答案，这种理解对于治疗牙周疾病至关重要。