GROWTH FACTORS AND GINGIVAL FIBROSIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objectives of this study are: 1. To determine the mechanisms of CTGF (Connective Tissue Growth Factor) activation of human gingival fibroblasts: identify functional domains of CTGF responsible for stimulating insoluble collagen accumulation, proliferation, and apoptosis. 2. To determine the mechanisms by which phenytoin increases CTGF levels in cultured human gingival fibroblasts: a) assess for deficient down-regulation of CTGF related to PGE2 and cAMP metabolism in gingival fibroblasts b) assess for phenytoin stimulated release of sequestered Smad's from microtubules, thereby increasing the level of CTGF transcription and expression. 3. Assay quantitatively human gingival tissue samples in situ to investigate in vivo the mechanisms and role of DTGF in contributing to inherited and drug-induced gingival overgrowth: a) measure the concentration of apoptotic cells, and proliferating cells, b) measure the expression of CTGF protein by quantitative methods and c) measure by quantitative immunohistochemistry PGE2 receptors d) measure the degree of fibrosis, and inflammation. All measurements will be performed in serial sections of the same tissues in inherited and drug-induced gingival overgrowth tissue samples compared to non-overgrown control gingival tissues. 250 subjects (12-65 years old) will be enrolled in the study. Patients undergoing routine periodontal flap surgery, crown lengthening procedures or surgery for impacted third molars will be enrolled in a control group. Patients undergoing gingivectomy surgery to treat gingival overgrowth will be recruited for the other four gingival overgrowth groups. All patients will be recruited from Boston University School of Dental Medicine, Boston University Medical Center, and affiliated hospitals and dental centers. Approximately 50 patients in each group will be enrolled during the 5 years. The study groups are as follows: 1. No gingival overgrowth (people undergoing routine periodontal or oral surgeries) 2. Phenytoin-induced gingival overgrowth 3. Cyclosporin A induced gingival overgrowth 4. Nifedipine-induced gingival overgrowth 5. Hereditary gingival overgrowth