Responses of the Temporomandibular Disk and of MG-63 Osteosarcoma Cell, a Model System, to Hydrostatic Pressure. In 1990, incidences of chronic pain due to temporomandibular joint dysfunction exceeded that of low back pain. Approximately one in nine people will be some type of pathology in their temporomandibular joints during their lifetime and each year over a billion dollars are spent by patients seeking treatment for temporomandibular disease. Yet little is understood about the normal molecular joint architecture, the changes that preceed clinical pathology, or the mechanisms of disease progression. In particular, the molecular basis for resistance to compressive loads in biological tissues such as the temporomandibular disk fibrocartilage is not well understood. It has been proposed that the glycosaminoglycans in the temporomandibular disk provide the basis for resistance to compressive loading because of their large hydration spheres. The first goal of the proposed research is to determine if the ability of habitually loading areas of the disk to resist compressive loads is primarily due to the increased levels of sulfation of the glycosaminoglycans, thus providing an increased density of fixed negative charges that slows the motional properties of the water. The second goal is also related to the ability of the disk to respond to mechanical loads or changes in mechanical loads. Because the disk is a fibrocartilage with a very low cell density, the mechanical properties of the tissue are primarily dependent on the composition of the extracellular matrix. Although the gross physical effects of mechanically loading a tissue are generally known, the cellular and molecular responses to physical loading are not well understood. The second goal is to determine if the remodeling activity seen in pressure responsive tissue subjected to mechanical forces involves alterations in integrin gene expression.
The specific aims are: 1. Determine the elemental content (S, K, Na, Cl, P, Mg, and Ca) by x-ray microanalysis and correlate variation in elemental content with varitation in resistance to fluid flow during centrifugal loading of individual areas of the TMJ disk. 2. Determine the extent of water of hydration compartments in the TMJ fibrocartilage using nuclear magnetic resonance techniques and assays of water holding capacity when subjected to defined forces. 3. Determine if altered integrin expression in response to hydrostatic pressure results in altered cytoskeletal and extracellular matrix organization in MG-63 osteosarcoma cells as assayed by immunohistochemistry. 4. Determine if integrin gene expression is differentially regulated by hydrostatic pressure in MG-63 osteosarcoma cells using a reverse transcription-polymerase chain reaction assay.
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