A Research Center in Oral Biology (RCOB) is proposed with the overall goal of understanding mechanisms of development and remodeling in two tissues important for craniofacial and dental health, bone and gingiva. These tissues have in common the property of being extremely dynamic. Excessive remodeling of gingiva can lead to its recession and to both tooth and bone loss. Birth defects, trauma and aging cause defects in or destruction of the craniofacial skeleton. Successful treatment or prevention of excessive gingival remodeling and bone loss is currently hampered by a lack of basic understanding of the roles played by molecules involved in generating and regulating extracellular matrix production and degradation. The projects in this proposal focus on the molecular basis of cell-extracellular matrix interactions and how they are regulated to establish and maintain appropriate tissue architecture in gingival tissue and bone. The classes of molecules studies are: extracellular matrix components and their cell surface receptors, matrix- degrading proteinases and their inhibitors, and members of the TGF-beta family, which play an important role in their regulation. Project I studies the extracellular matrix region of gingival re-epithelialization following wounding, using both cultured keratinocytes and samples of healing wounds. Project 2 studies the effects of volatile sulfur gases (VSC) on gingival extracellular matrix integrity and on the function of gingival fibroblasts and keratinocytes. The VSC are of the type released in periodontal disease, and the project is thus investigating a model for chronic """"""""chemical wounding"""""""" of the periodontium. Project 3 addresses the hypothesis that extracellular matrix interactions with specific cell- surface adhesion receptors are critical in promoting osteoblastic differentiation, utilizing a newly isolated pluripotential mesenchymal stem cell line. Project 4 addresses the role of a newly characterized member of the TGF-beta family, vgr-1 (BMP-6), in osteoblast differentiation. Project 5 utilizes an in vitro model of first branchial arch differentiation to determine how proteinases and their inhibitors contribute to the differentiation and patterning of the mandible. Two pilot projects address the mechanism of interaction of a periodontal pathogen with extracellular matrix, and stress-induced remodeling of bone. Administrative, Molecular Biology and Morphology cores are requested to support the Center's research activities. This proposed RCOB brings together investigators with common interests, but varied expertise that includes state-of-the-art molecular, cell biological, and immunochemical approaches. The RCOB will also serve as an excellent vehicle to train graduate students in the Oral Biology Graduate Program, and to mentor young investigators through the use of pilot projects.
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