MECHANISMS OF GLUCOCORTICOID-GROWTH FACTOR INTERACTIONS

除了预防，限制疾病进展和诱导 失去的组织的再生是现代医学的两个最重要的目标。 牙周治疗 本建议分两部分论述这两个问题。 问题 第一部分旨在探讨 糖皮质激素诱导的血小板衍生生长因子（PDGF）协同作用 体外有丝分裂。 一种治疗组合，其包含PDGF和 与不溶性胶原蛋白基质复合的地塞米松能够 诱导牙周组织再生。 很可能在体内 PDGF/Dex提供初始分子信号，诱导有能力的细胞， 增殖、迁移，随后引发复杂的级联反应， 最终导致组织再生的事件。 机制 Dex对PDGF有丝分裂的协同作用尚不清楚。 因此，本提案将探讨生物化学和分子基础 对于地塞米松对PDGF有丝分裂的协同作用， 体外 利用二倍体人牙龈和牙周的菌株 韧带成纤维细胞，拟议的实验将确定是否Dex 影响细胞的循环分数或通过 细胞周期 通过实验确定可能的生化机制， 哪些激素和生长因子可以相互作用来调节 和/或循环分数的速率 扩散计划。 分子基础的操作 生物化学途径将使用现代技术进行探索， 分子生物学 第二部分旨在研究四环素类药物对 体内结缔组织降解，使用结扎诱导的模型， 非人类灵长类的牙周炎。 四环素类药物长期以来一直被用于 作为治疗牙周病的药物， 抗菌作用，其独特的能力，非抗菌 这些性质也是治疗上有利的。 这些包括 四环素直接抑制宿主胶原溶解酶的能力 从而抑制包括骨在内的结缔组织降解 吸收，其表征多种疾病过程，包括 牙周病 这项研究的长期目标是 表明四环素类，包括化学修饰的 四环素，缺乏抗菌性能，可以防止或阻碍 牙周病 全身给药的影响 四环素类药物对结扎引起的牙周炎的进展将 使用猴的临床和生化参数进行监测 接种牙龈卟啉单胞菌。

Next to prevention, limiting disease progression and inducing regeneration of lost tissues are the two most important goals of modern periodontal therapy. This proposal, in two parts, deals with these two problems. The first part intends to explore the mechanisms of action of glucocorticoid induced synergy of platelet-derived growth factor (PDGF) mitogenesis in vitro. A therapeutic combination comprised of PDGF and dexamethasone complexed in an insoluble collage matrix is capable of inducing regeneration of the periodontium. It is likely that in vivo PDGF/Dex provides an initial molecular signal inducing capable cells to proliferate, migrate and subsequently initiate a complex cascade of events which ultimately results in tissue regeneration. The mechanism for the synergistic effect of Dex on PDGF mitogenesis is not clear. Therefore this proposal will explore the biochemical and molecular basis for the synergistic effect of dexamethasone on PDGF mitogenesis, in vitro. Utilizing strains of diploid human gingival and periodontal ligament fibroblasts, the proposed experiments will determine if Dex affects the cycling fraction of cells or the rate of transit through the cell cycle. Experiments to determine possible biochemical mechanisms by which hormones and growth factors may interact to regulate the fraction of cells proliferating and/or the rate at which the cycling fraction proliferates are planned. The molecular basis of the operative biochemical pathway(s) will be explored using the modern techniques of molecular biology. The second part intends to study the effects of tetracyclines on connective tissue degradation in vivo, using a ligature induced model of periodontitis in non-human primates. Tetracyclines have long been used as adjuncts for the treatment of periodontal disease because of their antimicrobial effects, their unique ability to non-antimicrobial properties that are also therapeutically advantageous. These include the tetracycline ability to directly inhibit host collagenolytic enzymes thereby inhibiting connective tissue degradation, including bone resorption, that characterizes a variety of disease processes including periodontal disease. The long-term goal of this research is to demonstrate that tetracyclines, including the chemically modified tetracycline, devoid of antimicrobial properties, can prevent or impede periodontal breakdown. The effects of systemically administered tetracyclines on the progression of ligature induced periodontitis will be monitored using both clinical and biochemical parameters in monkeys inoculated with Porphyromonas gingivalis.