GROWTH FACTORS AND GINGIVAL FIBROSIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。本研究的目的是：1.确定结缔组织生长因子(CTGF)激活人牙龈成纤维细胞的机制：确定CTGF的功能结构域，促进不溶性胶原的积累、增殖和凋亡。2.探讨苯妥英钠增加培养的人牙龈成纤维细胞CTGF水平的机制：a)检测与PGE2和cAMP代谢相关的CTGF表达下调；b)检测苯妥英钠刺激微管中孤立的Smad的释放，从而提高CTGF的转录和表达水平。3.原位定量检测人牙龈组织标本，探讨DTGF在遗传性和药物诱导的牙龈过度生长中的作用机制：a)检测细胞凋亡和增殖细胞的浓度；b)定量检测CTGF蛋白的表达；c)免疫组织化学定量检测PGE_2受体的表达；d)检测纤维化和炎症的程度。所有测量将在遗传性和药物诱导的牙龈过度生长组织样本中的相同组织的连续切片中进行，与非过度生长的对照牙龈组织相比较。250名受试者(12-65岁)将参加这项研究。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。接受牙龈切除手术以治疗牙龈过度生长的患者将被招募到其他四个牙龈过度生长组。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及其附属医院和牙科中心招募。每组约50名患者将在5年内入选。研究小组如下：1.无牙龈过度生长(接受常规牙周或口腔手术的人)2.苯妥英引起的牙龈过度生长3.环孢素A引起的牙龈过度生长4.硝苯地平引起的牙龈过度生长5.遗传性牙龈过度生长

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