We seek support for the development and operation of an interdisciplinary Research Center in Oral Biology. The purpose of the Center is to assist in the national effort to reduce the toll of oral disease, and to promote the general level of oral health. The Center seeks to create a research environment of excellence, to attract investigators of high quality into dental research, to provide challenging opportunities for research training and to foster research-related relationships with other institutions. Our efforts focus on Oral Tissue Repair and Regulation, with specific attention paid to mechanisms of regulation of cell growth and synthesis, and regeneration of periodontal attachment. Our concepts and technologies are drawn from the forefront of modern molecular and cell biology. We will elucidate mechanisms whereby binding of complement components activates growth by a unique population of fibroblasts that may participate in regeneration. We will define the molecular mechanism of regulation of selected growth-associted genes and demonstrate the mechanism of linkage to transmembrane signals. Using the B lymphocyte as a model system, we will more precisely define the site and mode of action of signals that downregu- late cell growth. In order to obtain new information about regulation of synthesis of matrix molecules, we will use transfected cells and cell-free systems to identify specific DNA sequences in or near the genes for type I collagen and thrombospondin that serve as positive or negative regulatory sequences, and isolate and characterize DNA binding proteins that interact with these sequences. The unique union between the teeth and the soft tissue is mediated by the junctional epithelium which is joined on one side to root cementum and on the other to the supporting connective tissue. In spite of their importance, the junctional epithelium, cementum, and proteoglycan component of the extracellular matrix remain the least studied and most poorly understood of all oral structures. We will characterize th growth and synthetic properties of junctional epithelial cells, and assess the effects of noxious agents with which they come into contact. We will characterize growth and attachment factor/s in human cementum that have profound effects on fibroblast growth and synthesis, and elucidate the mechanisms by which they operate. Using gingival fibroblasts maintained in differing states of growth, we will evaluate the hypothesis that the type and quantity of proteoglycan produced is coupled to growth state. Successful completion of the studies will provide a new fundamental understanding about how oral tissues heal and regenerate.
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