Estrogen Negatively Modulates Proteoglycan-4 Expression in TMJ

雌激素负向调节 TMJ 中蛋白多糖 4 的表达

基本信息

批准号：
9130839
负责人：
Richard Gordon LeBaron
金额：
$ 10.69万
依托单位：
UNIVERSITY OF TEXAS SAN ANTONIO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9130839
关键词：
5&apos Flanking Region Accounting Adherent Culture Affect American Attenuated Binding Biological Assay Biological Sciences Biology Biomedical Research Birth Cartilage Cells Comorbidity Conditioned Culture Media Critiques Data Development Dislocations Down-Regulation Employee Strikes Environment Enzyme-Linked Immunosorbent Assay Estradiol Estrogen Receptor beta Estrogens Event Extracellular Matrix Facial Pain Failure Female Female of child bearing age Friction Gender Gene Expression Gene Expression Regulation Gene Proteins Genes Genetic Transcription Glenoid structure Goals Gonadal Steroid Hormones Head Health Human Immunoblotting In Situ In Vitro Individual Joints Knowledge Lead Lubrication Maintenance Mandibular Condyle Mediating Mentors Messenger RNA Molecular Mutation Papio Pathogenesis Pathology Patients Phenotype Play Population Prevalence Promoter Regions Protein Isoforms Proteoglycan Publishing RNA Splicing Regulation Reporter Genes Reporting Research Research Training Response Elements Role Structure of articular disc of temporomandibular joint Synovial Cell Synovial Membrane System Temporal bone structure Temporomandibular Joint Temporomandibular Joint Disorders Testing Therapeutic Time Tissues Translating Underrepresented Students Work attenuation base cartilage cell chromatin immunoprecipitation effective therapy gender disparity innovation insight joint function knowledge base male molecular pathology promoter receptor sex sexual dimorphism training opportunity

项目摘要

DESCRIPTION (provided by applicant): Temporomandibular joint disorders (TMDs) affect a significant portion of the population of the USA, with the majority of those seeking treatment being women of childbearing age. Owing to this striking sexual dimorphism it has been postulated that sex hormones play a role in the maintenance of normal temporomandibular joint (TMJ) function. Proteoglycan 4 (PRG4) is a secreted lubricating molecule essential for maintaining low frictional levels within articular joints; however, its role in the TMJ is not well characterized. We identified conserved estrogen response elements within the 5' flanking region of the PRG4 gene of human and baboon, and found that treatment of baboon TMJ disc cells with estrogen attenuated PRG4 promoter activity and expression of PRG4 mRNA in vitro. This discovery of negative regulation of PRG4 by estrogen is the basis for the hypothesis that a causative event in the development of TMD is estrogen-mediated down regulation of PRG4 transcription. Insufficient quantity of PRG4 in the TMJ is expected to lead to increased friction and over time, degradation of TMJ components affecting the articulation of the mandibular condyle with the glenoid fossa of the temporal bone and disc placement, which largely describes the human TMD phenotype. In this study we propose three specific aims; 1) to determine the extent that estrogen decreases PRG4 expression in female and male baboon TMJ cells and TMJ organotypic cultures. Immunoblots and qPCR will be used to quantify estrogen effects on PRG4 expression in synovial and cartilage cells and tissues that will be compared to PRG4 expression in TMJ disc cells and tissue. 2) To characterize by ChIP analysis estrogen alpha and beta receptors and estrogen response element binding in PRG4 gene regulation in femal and baboon TMJ cells. 3) To provide a highly mentored environment and rigorous biomedical research training opportunities for the development of underrepresented students in the life sciences.

描述：颞下颌关节疾病（TMD）会影响美国寻求治疗的人的大部分是育龄的妇女（PRG4）。它在TMJ中的作用不好表征我们。体外，通过假设TMD的事件对PRG4的负调节是雌激素介导的prg4转录。随着时间的流逝，TMJ成分的降解在本研究中提出的特定目的是，在本研究中，颞骨和椎间盘放置的腹腔脉络TMJ器官培养物。 Femal Baboon TMJ中的基因调节3）A A LEF的远景学生的高度受过良好的环境研究培训机会。