CELLULAR AND MOLECULAR TARGETING OF TMJ DESTRUCTION

University Of Tennessee Health Sci Ctr, Memphis TN

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Abstract

DESCRIPTION: The overall objective of this proposal is to understand the biological and molecular basis of TMJ destruction via synovial fibroblasts and MMP pathway. The proposal has three specific Aims. In Aim I, production levels of MMP-2, MMP-3 and their inhibitors, TIMP-1 and TIMP-2, by fibroblasts obtained from diseased human TMJ will be measured. Measurement will be by ELISAs of conditioned media and, by using different assay kits, total and active MMP-levels will be determined. Levels in cells treated with and without IL-1b will be compared; the objective is to determine if diseased TMJ fibroblasts have exaggerated response to the IL-1b. Tissue sections will be analyzed by immunohistochemistry to localize MMP-2, MMP-3, TIMP-1 and TIMP-2. In Aim II, the conditioned media from IL-1b treated and untreated cultures will be assayed for active MMP-2 and MMP-3 using commercially available assay kits. In Aim III, MMP production and activities will be correlated with the degree of TMJ destruction using the method of "Bronstein and Merrill arthroscopic staging correlated with Silkes' Staging Method." Correlation will take into account five stages of TMJ destruction, duration of disease and symptoms. It is hoped that completion of these three aims will provide a detailed knowledge of the biological basis of TMJ destruction via synovial fibroblasts and MMP pathway.