GROWTH FACTORS AND GINGIVAL FIBROSIS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究的目的是：1.确定CTGF（结缔组织生长因子）激活人牙龈成纤维细胞的机制：确定CTGF负责刺激不溶性胶原积累、增殖和凋亡的功能结构域。 2.为了确定苯妥英增加培养的人牙龈成纤维细胞中CTGF水平的机制：a）评估牙龈成纤维细胞中与PGE 2和cAMP代谢相关的CTGF下调不足B）评估苯妥英刺激的从微管中释放隔离的Smad，从而增加CTGF转录和表达水平。3.原位定量测定人牙龈组织样品以研究DTGF在促进遗传性和药物诱导的牙龈过度生长中的体内机制和作用：a）测量凋亡细胞和增殖细胞的浓度，B）通过定量方法测量CTGF蛋白的表达和c）通过定量免疫组织化学PGE 2受体测量d）测量纤维化和炎症的程度。所有测量将在遗传性和药物诱导牙龈过度生长组织样本与非过度生长对照牙龈组织相同组织的连续切片中进行。 本研究将入组250例受试者（12-65岁）。接受常规牙周瓣手术、牙冠延长术或阻生第三磨牙手术的患者将被纳入对照组。接受牙龈切除术治疗牙龈增生的患者将被招募到其他四个牙龈增生组。所有患者将从波士顿大学牙科医学院、波士顿大学医学中心以及附属医院和牙科中心招募。在5年期间，每组将入组约50例患者。研究组如下：1.无牙龈增生（接受常规牙周或口腔手术的人）2.苯妥英钠诱导牙龈增生3.环孢菌素A诱导牙龈增生4.硝苯地平诱导牙龈增生5.遗传性牙龈增生

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