Molecular Basis of Tooth Eruption

牙齿萌出的分子基础

基本信息

批准号：
8277789
负责人：
Shaomian Yao
金额：
$ 34.94万
依托单位：
LOUISIANA STATE UNIV A&M COL BATON ROUGE
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8277789
关键词：
Affect Alveolar Alveolar Bone Loss Bone Growth Bone Resorption Cell fusion Cells Coculture Techniques Coupled Dendritic Cells Dental Sac Disease Down-Regulation Electroporation Event Excision Gene Expression Genes Goals Impacted Tooth Incubated Injection of therapeutic agent Integral Membrane Protein Macrophage Colony-Stimulating Factor Messenger RNA Methods Mind Molecular Osteoblasts Osteoclasts Osteogenesis Pathway interactions Periodontal Ligament Periodontitis Population Progeria Proteins RNA Interference Regulation Reverse Transcriptase Polymerase Chain Reaction Role Scanning Electron Microscopy Small Interfering RNA Stem cells Syndrome TNFSF11 gene Technology Testing Time Tooth eruption Up-Regulation Vascular Endothelial Growth Factors alveolar bone base bone morphogenetic protein 2 frizzled related protein-1 in vivo laser capture microdissection osteoclastogenesis osteogenic precursor cell prevent stem cell differentiation

项目摘要

Project Summary. Tooth eruption requires alveolar bone resorption and bone formation. We have shown that the osteoclastogenesis needed for resorption of alveolar bone in the coronal region of the bony crypt is regulated by expression of osteoclastogenesis genes in the dental follicle (DF). Similarly, we hypothesize that osteo-inductive genes expressed in the DF, especially those genes upregulated in the basal one-half of the DF, promote tooth eruption by regulating the osteogenesis needed for bone formation that occurs at the base of the alveolar bony crypt. To test this hypothesis, gene microarray studies will be done to determine which osteo-inductive genes are upregulated in the DF at the times of maximal bone growth at the base of the socket. Next, because surgical removal of the basal one-half of the DF prevents tooth eruption and alveolar bone formation, laser capture microdissection coupled with real-time RT-PCR studies will determine which of these osteo-inductive genes are expressed more in the basal portion than in the coronal portion of the DF. Each gene that is upregulated more in the basal portion will then be silenced in vivo using electroporation and RNAi technology specific for the target mRNA of each gene to determine the effect of each gene on eruption times. Regarding osteoclastogenesis, secreted frizzled-related protein-1 (SFRP-1), a molecule that inhibits osteoclastogenesis, is expressed in the DF and it is hypothesized that its gene expression is downregulated by eruption molecules such that osteoclastogenesis can occur. Thus, DF cells will be incubated with molecules that promote osteoclastogenesis for eruption to determine which of them down-regulate SFRP-1 expression. Using osteoclast precursor cells, we also will determine if SFRP-1 inhibits osteoclastogenesis by down- regulating a cell fusion molecule, DC-STAMP. Finally, we hypothesize that stem cells present in the DF might contribute to the osteoclast precursors and osteoblasts needed for eruption. To test this, stem cells isolated from the DF will be incubated with osteoclast-inducing molecules or with osteo-inductive molecules to determine if the stem cells can form osteoclasts or osteoblasts. Relevance. Understanding the molecular regulation of the osteogenesis and osteoclastogenesis needed for eruption may explain why impacted teeth (e.g., 3rd molars) do not erupt, as well as explain the causes of various eruption disorders such as seen in Hutchinson-Gilford Progeria syndrome. To correct eruption disorders, a molecular approach to induce eruption is a long-term goal. Finally, because the periodontal ligament (PDL) is derived from the DF, the molecular regulation of osteoclastogenesis by the DF may suggest a similar role for the PDL in regulating alveolar bone loss seen in periodontitis.

项目摘要。牙齿萌出需要牙槽骨吸收和骨形成。我们已经证明骨隐窝冠状区牙槽骨吸收所需的破骨细胞生成是受牙囊（DF）中破骨细胞生成基因表达的调节。同样，我们假设骨诱导基因在 DF 中表达，特别是那些在基底二分之一中上调的基因 DF，通过调节基底部骨形成所需的成骨作用来促进牙齿萌出的牙槽骨隐窝。为了检验这一假设，将进行基因微阵列研究以确定哪些当骨基部骨生长最大时，DF 中的骨诱导基因上调插座。其次，因为手术切除 DF 基底的一半可以防止牙齿萌出和牙槽骨骨形成、激光捕获显微切割结合实时 RT-PCR 研究将确定哪些这些骨诱导基因在 DF 的基底部分比在冠状部分表达更多。然后，使用电穿孔在体内沉默每个在基底部分上调更多的基因，并特异针对每个基因的靶mRNA的RNAi技术，以确定每个基因对萌发的影响次。关于破骨细胞生成，分泌型卷曲相关蛋白 1 (SFRP-1)，一种抑制破骨细胞生成的分子破骨细胞生成在 DF 中表达，推测其基因表达被下调萌发分子，从而可以发生破骨细胞生成。因此，DF 细胞将与分子一起孵育促进破骨细胞生成以测定萌发，以确定其中哪些下调 SFRP-1 表达。使用破骨细胞前体细胞，我们还将确定 SFRP-1 是否通过下调抑制破骨细胞生成。调节细胞融合分子 DC-STAMP。最后，我们假设 DF 中存在的干细胞可能有助于形成萌出所需的破骨细胞前体和成骨细胞。为了测试这一点，分离了干细胞来自 DF 的分子将与破骨细胞诱导分子或骨诱导分子一起孵育，确定干细胞是否可以形成破骨细胞或成骨细胞。关联。了解成骨和破骨细胞生成所需的分子调控萌出可以解释为什么阻生牙（例如，第三磨牙）不萌出，以及解释以下原因：各种发疹性疾病，例如哈钦森-吉尔福德早衰综合症。纠正喷发对于疾病，诱导萌发的分子方法是一个长期目标。最后，因为牙周韧带（PDL）源自 DF，DF 对破骨细胞生成的分子调节可能表明 PDL 在调节牙周炎中观察到的牙槽骨丢失方面发挥着类似的作用。

项目成果

期刊论文数量（60）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Evaluation of bone regeneration potential of dental follicle stem cells for treatment of craniofacial defects.

DOI：
10.1016/j.jcyt.2015.07.013
发表时间：
2015-11
期刊：
Cytotherapy
影响因子：
4.5
作者：
Rezai-Rad M;Bova JF;Orooji M;Pepping J;Qureshi A;Del Piero F;Hayes D;Yao S
通讯作者：
Yao S

The role of dentin matrix protein 1 (DMP1) in regulation of osteogenic differentiation of rat dental follicle stem cells (DFSCs).

DOI：
10.1016/j.archoralbio.2014.12.013
发表时间：
2015-04
期刊：
ARCHIVES OF ORAL BIOLOGY
影响因子：
3
作者：
Rad, Maryam Rezai;Liu, Dawen;He, Hongzhi;Brooks, Hunter;Xiao, Mei;Wise, Gary E.;Yao, Shaomian
通讯作者：
Yao, Shaomian

Chronological gene expression of parathyroid hormone-related protein (PTHrP) in the stellate reticulum of the rat: implications for tooth eruption.