Estrogen Receptor Beta Regulation of Mandibular Condylar Growth

雌激素受体β对下颌髁突生长的调节

• 批准号: 8311239
• 负责人: Sunil Wadhwa
• 金额: $ 18.39万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311239
• 关键词: Affect; Age; Cartilage; Cells; Chondrocytes; Chondrogenesis; Data; Degenerative Disorder; Differentiation and Growth; Disease; Equilibrium; Estrogen Receptor beta; Estrogens; Female; Female of child bearing age; Gender; Gene Expression; Genes; Genetic; Goals; Growth; Hour; Incisor; Joints; Lead; Length; Mandible; Mandibular Condyle; Measurement; Mechanical Stress; Mechanics; Mediating; Modeling; Mus; Natural regeneration; Oral cavity; Osteogenesis; Ovariectomy; Periosteum; Population; RNA; Regulation; Research; Role; Soft Diet; Staging; Temporomandibular Joint; Temporomandibular Joint Disorders; Testing; Thick; Time; Tissues; Weight-Bearing state; Width; Woman; Work; condylar cartilage; in vivo; innovation; insight; male; mouse model; novel strategies; outcome forecast; public health relevance; regenerative therapy; research study; response; skeletal; young adult

DESCRIPTION (provided by applicant): The long-term goal of our research is to understand the mechanisms regulating growth and differentiation of mandibular condylar cartilage. The mandibular condylar cartilage is derived from periosteum and comprised of 4 zones that contain cells at various stages of endochondral ossification. The mandibular condylar cartilage remodels in response to external mechanical strains by regulating chondrogenesis and endochondral ossification, in order to achieve a better balance between mechanical stress and the load bearing capacity of the joint. Estrogen regulates mandibular condylar cartilage growth and differentiation. It is known that the estrogen-mediated inhibition of mechanical loading-induced periosteal bone formation and axial skeletal growth requires estrogen receptor beta (ER¿). However, the mechanisms underlying the regulatory effects of estrogen in the mandibular condylar cartilage remain unknown. The general objective of this application is to examine the effects of estrogen status on the regulation of mandibular condylar cartilage growth induced by mechanical loading. Our central hypothesis is that estrogen acts through ER¿ to inhibit chondrocyte maturation in the mandibular condylar cartilage in female mice and will, therefore, affect the response of condylar cartilage to mechanical stress. To test this hypothesis, the following Specific Aims will be examined; Specific Aim 1: Examine mandibular condylar growth in ER¿ deficient mice. Basal Mandibular condylar cartilage growth and differentiation in male and female wild type (WT) and ER2 deficient mice will be assessed. In addition, mandibular condylar growth will be examined in sham or ovariectomized WT and ER¿ deficient mice treated with or without estrogen. Specific Aim 2: Examine the role of ER¿ in the regulation of mandibular condylar cartilage differentiation in TMJ loading models. Two in vivo TMJ mechanical loading models, which cause either an increase or a decrease in mandibular chondrocyte differentiation, will be applied to male and female WT and ER¿ deficient mice. Mandibular condylar growth and differentiation will be assessed from both models. Greater understanding on how mandibular condylar cartilage remodeling is controlled by estrogen and mechanical loading will aid in the understanding of diseases of the temporomandiblar joint (TMD), which have a predilection for women between the ages of 18 and 45, and may also lead to new approaches to joint regeneration. PUBLIC HEALTH RELEVANCE: Approximately, 10% of the United Sates population has suffered from temporomandibular joint disorders (TMD). TMD predominantly affects women of childbearing ages, but the reasons behind this are unknown. This proposal examines the mechanism behind estrogen inhibition of growth and differentiation of the mandibular condylar cartilage, which will give further insight into the age and gender predilection of TMD.

描述（通过应用程序提供）：我们研究的长期目标是了解调节下颌con骨软骨的生长和分化的机制。下颌骨对照道软骨源自骨膜，并完成4个区域，这些区域在内侧软骨骨化的各个阶段都包含细胞。下颌骨软骨通过控制软骨发生和内软骨骨化而响应外部机械菌株的重塑，以在机械应力与关节的负载能力之间取得更好的平衡。雌激素调节下颌对道软骨的生长和分化。众所周知，雌激素介导的机械负荷诱导的骨膜骨形成和轴向骨骼生长的抑制需要雌激素受体β（ER？）。然而，雌激素在下颌对道软骨中的调节作用的基础机制尚不清楚。该应用的一般目的是检查雌激素状态对机械负荷引起的下颌对道软骨生长的调节的影响。我们的中心假设是，雌激素通过ER抑制雌性小鼠的下颌do骨软骨中软骨细胞的成熟，因此会影响孔道软骨对机械胁迫的反应。为了检验这一假设，将检查以下特定目标；特定目标1：检查不足小鼠ER的下颌con孔生长。将评估男性和雌性野生型（WT）和ER2缺乏小鼠的基础下颌对照软骨的生长和分化。此外，将在假性或卵巢的WT和ER eR中检查下颌骨生长，并在接受或没有雌激素治疗的情况下进行缺乏小鼠。具体目的2：检查ER？在TMJ载荷模型中下颌do骨软骨分化中的作用。两个体内TMJ机械载荷模型，这会导致下颌软骨细胞分化的增加或减少，将应用于雄性和雌性WT和ER不足的小鼠。下颌condolar的生长和分化将从两个模型中评估。对下颌dy子软骨重塑如何通过雌激素控制和机械负荷控制将有助于理解颞关节疾病（TMD），这对18至45岁的女性的预测也可能导致关节再生的新方法。 公共卫生相关性：大约有10％的联合国人口患有颞下颌关节疾病（TMD）。 TMD主要影响生育年龄的妇女，但其原因是未知的。该提案检查下颌con养育软骨生长和分化的雌激素抑制背后的机制，这将进一步了解TMD的年龄和性别预测。