In the proposed research, the pathogenic mechanism(s) of intraosseous bone destruction which occurs during the development of periapical lesions will be elucidated. A rat model system will be employed in which periapical lesions are induced by pulp exposure and infection from the oral environment. Lesion development occurs with highly reproducible kinetics, and the phase of active expansion is precisely delineated from a chronic phase characterized by relative lesion stability. Periapical tissues will be isolated at various times after induction, and the total bone resorbing activity (BRA) which is present will be quantitated using the fetal long bone assay. The timing of the active and chronic phases will be confirmed using radiopharmaceutical uptake and radiography. BRA attributable to bacterial lipopolysaccharide (LPS) will be quantitated by inhibition with polymyxin B, IL-1 and PGE2 will be measure by radioimmunoassay, and LT will be quantitated in a microcytotoxicity assay. The levels of IL-1, LT, PGE2 and LPS will be correlated with the active phase of lesion formation and total bone resorbing activity. Further confirmation for the role of one of these candidate mediators in lesion pathogenesis will be obtained in in vivo studies using specific inhibitors of cytokines and prostaglandins. These studies comprise a directed analysis of the mechanism of inflammatory bone destruction in a well-defined animal model system.
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