Little information exists regarding the role of specific bacterial components as virulence factors in oral disease processes. Among the large number of bacteria found in the inflammatory diseases of periodontal origin, several have been made frequently found associated with disease; these are Bacteroides, Eikenella, Wolinella, and Actinobacillus. Whole cell inoculation of these genera into gnotobionts results in bone resorption. Several lippolysaccharides (LPS), peptidoglycans (PG), and outer membranes of these genera possess an ability to induce net bone resorption in organ culture. Whether this is due to activation of osteoclasts or to inhibition of osteogenesis is unknown. Why one component is cytotoxic, or induces bone loss and why another is either low or devoid of activity is unknown. Which are the active chemical constituents of these molecules is also unknown. This project examines whether the net bone resorption associated with these virulence factors is due in part to inhibition of osteoblast activity, and if so, determines which component subunits of these factors produces this response. the studies proposed will: 1. localize by immunomicroscopy collagenase, and aminopeptidase in oral pathogens, and localize outer membrane vesicles in biopsy gingival oral epithelium from primates in which periodontitis has been induced; 2. compare the chemistry of the LPS and PG from these pathogens; and 3. determine whether these molecules and their subunits are effective resorbing molecules of bone as well as being able to alter bone formation; as well as determining the biochemical mechanisms by which osteoblast metabolism is altered. Activation of specific tissue destructive lysosomal hydrolases in osteoblast cell lines as well as inhibition of osteogenic activity will be determined. These studies will extend our understanding of the role of specific chemical constituents of bacterial macromolecules as virulence factors, and provide for future studies to design rationales for protection of the host against these bacterial virulence factors.
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