Estrogen Negatively Modulates Proteoglycan-4 Expression in TMJ

Research project

Description

? 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.
StatusActive
Effective start/end date9/1/158/31/19

Funding

  • National Institutes of Health: $95,972.00
  • National Institutes of Health: $106,941.00

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Temporomandibular Joint
Proteoglycans
Estrogens
Papio
Temporomandibular Joint Disorders
Temporomandibular Joint Disc
Response Elements
Genes
Tissue
Mandibular Condyle
Estrogen Receptor beta
Biological Science Disciplines
Friction
Estrogen Receptor alpha
Temporal Bone
5' Flanking Region
Gonadal Steroid Hormones
Cartilage
Biomedical Research
Down-Regulation

Keywords

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)