Periodontitis is a chronic infectious disease process which is highly prevalent in human populations. Although periodontitis is most common in adults, several forms of early onset periodontitis are seen in children and adolescents. An understanding of the basic biologic process leading to the formation of periodontal tissues during embryonic and childhood development, as well as their maintenance during adulthood is crucial doe the development of new approaches for the prevention, diagnosis and treatment of periodontitis. We have previously identified a pleiotropic cytokine called oncostatin M (OSM) (OSM) which is important in cell growth, regulation and differentiation during early development and maturation. We and others have shown that OSM acts as an anti- inflammatory molecule which has regenerative activities with regard to connective tissue and bone. We have recently demonstrated that OSM is expressed in gingival tissues in vivo and in vitro and that this expression is down-regulated by bacterial components. Furthermore, we have evidence that the OSM specific receptor is abundantly expressed in several periodontal cell types. Although considerable work remains to establish the function of OSM in oral tissues, our data suggest that OSM may be important for the development and maintenance of the normal periodontium. Our studies suggest that the induction of OSM in or the addition of exogenous OSM to periodontal tissues could reverse the disease progression in periodontitis. We believe that the proposed research may provide a basis for therapeutic testing of OSM in vivo preclinical and clinical trials. In addition, this research will further our understanding of childhood susceptibility to oral diseases, with the potential for the development of new therapeutic interventions. In this application, we propose the following specific aims: 1) Determine the expression levels of OSM in serum, gingival crevicular fluids and gingival biopsies from children and adults with periodontal disease. 2) Assess the ability of periopathogenic bacteria and induced pro-inflammatory mediators to module the expression of OSM and the OSM receptor subunits in gingival epithelial cell cultures in vitro. 3) Determine the effects of OSM on gingival fibroblast and epithelial cells in vitro by analyzing the expression of genes for various cytokines, chemokines, tissue-specific genes, and proteinases and their inhibitors which are implicated in periodontal disease.
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