MECHANISMS OF GLUCOCORTICOID-GROWTH FACTOR INTERACTIONS

仅次于预防、限制疾病进展和诱发 再生丢失的组织是现代医学的两个最重要的目标 牙周治疗。这项提案分为两个部分，涉及这两个问题 有问题。 第一部分意在探讨其作用机制。 糖皮质激素诱导的血小板衍生生长因子的协同作用 体外有丝分裂。由PDGF和PDGF组成的联合治疗 地塞米松在不溶性胶原蛋白基质中复合后能够 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 扩散、迁移并随后引发一系列复杂的 最终导致组织再生的事件。这一机制 地塞米松对PDGF有丝分裂的协同作用尚不清楚。 因此，这一建议将探索生物化学和分子基础。 关于地塞米松对PDGF有丝分裂的协同作用，在 体外培养。利用二倍体人牙龈和牙周组织菌株 韧带成纤维细胞，建议的实验将确定Dex 影响细胞的循环比例或通过 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能相互作用来调节这一比例 细胞增殖率和/或细胞周期分数 核扩散是有计划的。手术的分子基础 将使用现代技术探索生化途径(S) 分子生物学。 第二部分旨在研究四环素类药物对人体健康的影响。 结缔组织在体内的降解，使用结扎诱导的动物模型 非人灵长类的牙周炎。四环素类药物长期以来一直被使用 作为治疗牙周病的辅助药物，因为它们的 抗菌效果，其独特的非抗菌能力 对治疗也有好处的特性。这些措施包括 四环素直接抑制宿主胶原酶的能力 从而抑制结缔组织的降解，包括骨骼 吸收，这是各种疾病过程的特征，包括 牙周病。这项研究的长期目标是 证明四环素，包括化学修饰的 四环素，没有抗菌特性，可以预防或阻碍 牙周破裂。系统管理的影响 四环素类药物对结扎性牙周炎进展的影响 使用临床和生化参数对猴子进行监测 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.