Tooth Eruption: Role of Dental Follicle & PTH Receptor

牙齿萌出:牙囊的作用

基本信息

  • 批准号:
    6887375
  • 负责人:
  • 金额:
    $ 28.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

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,其中许多已经初步确定,但尚未明确。现有的证据表明,由牙囊区域内的细胞分泌的因子促进单核细胞的募集,以及它们分化成破骨细胞,随后牙槽骨吸收是牙齿萌出所需的。牙齿萌出的过程是功能性牙周膜(PDL)的发育。这种非矿化韧带的维持和功能性后萌出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,牙囊细胞具有甲状旁腺相关蛋白(PTHrP)的受体,并且PTHrP敲除小鼠具有缺陷性牙齿萌出的观察结果导致了这样的假设,即牙囊细胞是通过其PTHrP介导的刺激骨形成活性和抑制矿化而需要牙齿萌出的。三个具体的目标将测试这一假设使用在 体外和体内模型。第一个将定义PTHrP在PTH 1型受体(PTH-1 R)上对发育中牙齿微环境中细胞的作用,这些细胞被认为是促进破骨细胞分化和活化的。第二个目标将定义PTHrP在发育牙齿的微环境中的细胞上的PTH-1受体上的作用,所述作用被认为抑制矿化,从而维持功能性PDL并预防强直。最后,第三个目标将确定和特点的破骨细胞激活剂和矿化抑制剂的转录介质,促进牙齿萌出。通过鉴定牙齿萌出过程中PTHrP的介质和信号分子,这些研究将为确定牙齿萌出过程中的分子机制提供关键信息。这些有价值的信息将有助于设计治疗和预防策略,以解决导致咬合不正和口腔健康和功能受损的牙齿发育和萌出改变的条件。此外,这些研究将提高我们的基本知识,PTHrP和PTH-1 R的相互作用,在控制矿化组织的稳态的作用。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Laurie K. McCauley其他文献

Effects of transforming growth factor-α on parathyroid hormone- and parathyroid hormone-related protein- mediated bone resorption and adenylate cyclase stimulation in vitro☆
转化生长因子-α对甲状旁腺激素及甲状旁腺激素相关蛋白介导的骨吸收和体外腺苷酸环化酶刺激的影响☆
  • DOI:
    10.1016/0739-7240(91)90019-g
  • 发表时间:
    1991
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    T. Rosol;J. Merryman;R. Nohutçu;Laurie K. McCauley;C. Capen
  • 通讯作者:
    C. Capen
Skeletal metastasis: Established and emerging roles of parathyroid hormone related protein (PTHrP)
  • DOI:
    10.1007/s10555-006-9033-z
  • 发表时间:
    2006-12-13
  • 期刊:
  • 影响因子:
    8.700
  • 作者:
    Jinhui Liao;Laurie K. McCauley
  • 通讯作者:
    Laurie K. McCauley
Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism: Seventh Edition
代谢性骨疾病和矿物质代谢紊乱入门:第七版
  • DOI:
    10.1002/9780470623992
  • 发表时间:
    2009
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Clifford J. Rosen;J. Compston;J. Lian;R. Bouillon;S. J. Beur;S. Papapoulos;Pierre D. Delmas;Richard Keen;Vicki Rosen;M. Demay;Laurie K. McCauley;Ego Seeman;T. Guise;Paul D. Miller;R. V. Thakker
  • 通讯作者:
    R. V. Thakker
Prostate Carcinoma Skeletal Metastases: Cross-talk between Tumor and Bone
  • DOI:
    10.1023/a:1015599831232
  • 发表时间:
    2001-12-01
  • 期刊:
  • 影响因子:
    8.700
  • 作者:
    Evan T. Keller;Jian Zhang;Carlton R. Cooper;Peter C. Smith;Laurie K. McCauley;Kenneth J. Pienta;Russell S. Taichman
  • 通讯作者:
    Russell S. Taichman

Laurie K. McCauley的其他文献

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{{ truncateString('Laurie K. McCauley', 18)}}的其他基金

Repair of Bone Defects with Human Autologous Pluripotent Very Small Embryonic lik
人自体多能极小胚胎样修复骨缺损
  • 批准号:
    8394099
  • 财政年份:
    2012
  • 资助金额:
    $ 28.94万
  • 项目类别:
Biomimetics for craniofacial regeneration
颅面再生仿生学
  • 批准号:
    10374868
  • 财政年份:
    2012
  • 资助金额:
    $ 28.94万
  • 项目类别:
Biomimetics for craniofacial regeneration
颅面再生仿生学
  • 批准号:
    10005905
  • 财政年份:
    2012
  • 资助金额:
    $ 28.94万
  • 项目类别:
Integral role of hematopoietic cells in PTH actions in bone
造血细胞在骨 PTH 作用中的整体作用
  • 批准号:
    7684217
  • 财政年份:
    2008
  • 资助金额:
    $ 28.94万
  • 项目类别:
Integral role of hematopoietic cells in PTH actions in bone
造血细胞在骨 PTH 作用中的整体作用
  • 批准号:
    7556574
  • 财政年份:
    2008
  • 资助金额:
    $ 28.94万
  • 项目类别:
Integral role of hematopoietic cells in PTH actions in bone
造血细胞在骨 PTH 作用中的整体作用
  • 批准号:
    7932543
  • 财政年份:
    2008
  • 资助金额:
    $ 28.94万
  • 项目类别:
IMPACT OF PARATHYROID HORMONE (1-34) ON OSSEOUS REGENERATION IN THE ORAL CAVITY
甲状旁腺激素 (1-34) 对口腔骨再生的影响
  • 批准号:
    7603775
  • 财政年份:
    2007
  • 资助金额:
    $ 28.94万
  • 项目类别:
IMPACT OF PARATHYROID HORMONE (1-34) ON OSSEOUS REGENERATION IN THE ORAL CAVITY
甲状旁腺激素 (1-34) 对口腔骨再生的影响
  • 批准号:
    7199936
  • 财政年份:
    2005
  • 资助金额:
    $ 28.94万
  • 项目类别:
Bone Core
骨核
  • 批准号:
    8464641
  • 财政年份:
    2004
  • 资助金额:
    $ 28.94万
  • 项目类别:
PTHrP, Osteoblasts and Hematopoietic Cells in the Sketletal Metastic Niche
骨骼转移微环境中的 PTHrP、成骨细胞和造血细胞
  • 批准号:
    8377423
  • 财政年份:
    2004
  • 资助金额:
    $ 28.94万
  • 项目类别:

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