Epidemiological studies show that a large proportion of the population, particularly the elderly, have alterations in joint anatomy without having TMD. Furthermore, patients reporting signs of TMD, particularly pain, do not consistently have clinically observable alterations in joint anatomy. A significant obstacle to understanding of mechanisms of TMD pathology is the adequate models. The major aim of the following work is to characterize an animal model for temporomandibular dysfunction in humans, and to test possible mechanisms of initiation and progression in an appropriate cell culture system. The following three objectives are proposed: 1. Evaluate histology and immunohistochemistry of the temporomandibular joint in young vs. female baboons, and in normal vs. pathological joints. Much of the literature suggests that naturally occurring TMD is unique to man and this has impeded establishment of suitable animal models for experimental studies. Although previous investigations have characterized rabbit and rodent systems, it is difficult to extrapolate their significance for human disease due to differences in both form and function. Using standard histology and immunoperoxidase-monoclonal antibody techniques, the form and composition of the TMD joints from 7 young, 3, middle-age, and 8 old baboons have been characterized. 2. Evaluate the role of matrix hydration, fixed charge density and ion content to resistance to compressive load in the articular disk. The function of the fibrocartilage is dependent upon the intrinsic properties and organization of the major components of the disk. Collagen provides resistance to tensile and stretching forces. Proteoglycans (PG) are thought to provide resistance to compressive load by controlling matrix hydration. It is hypothesized that the PGs provides an increased density of fixed negative charges due to the sulfation of the glycosaminoglycans, thereby altering the hydration properties of the disk. X-ray microanalysis has bee used to determine the ion content of specific areas of the TMJ disk. NMR of progressively dehydrated tissue and freezing point depression have been used to determine the water of hydration of the TMJ disk. Movement of water of hydration under centrifugal force has been measured to determine the functional characteristics of the different water compartments. A model of explain the role of specific fixed charges and counterion in the hydration properties of the disk has been proposed. 3. Evaluate changes in cytoskeletal architecture and integrin profiles in response to hydrostatic pressure in MG-63 osteosarcoma cells. Integrins act as receptors for organized ECM components, interact with cytoskeletal components of the cell cytoplasm, and are active transduction of mechanical forces. It is thought that mechanical forces initiate remodeling in pressure responsive tissues due to increased hydrostatic pressure. Using direct immunofluorescence, we have demonstrated that there is loss of cytoskeletal organization and a heat shock like response following application of physiological ranges of hydrostatic pressure. Furthermore, using reverse transcription and polymerase chain reactions, we have demonstrated that there is a decrease in specific mRNAs consistent with a stress response.
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