Gene Expression in Chronic and Aggressive Periodontitis

产品说明：该研究项目的长期目标是促进牙周病患者的适当诊断，并最终成功治疗。虽然牙菌斑生物膜的特定细菌被认为是牙周炎的病因，但宿主对细菌挑战的可变免疫炎症反应在很大程度上被认为是疾病类型、程度和严重程度的关键决定因素。这种反应被认为有很强的遗传成分。目前，主要形式的牙周炎（慢性和侵袭性）的鉴别诊断主要是基于考虑医疗和口腔健康史后的临床体征。然而，这两种类型的疾病的临床表现可能非常相似，并且两者对标准治疗程序的反应可能差异很大。重要的是，慢性牙周炎和侵袭性牙周炎之间的区别的生物学基础还没有得到很好的证明。 拟议的项目是基于这样一种假设，即不同形式的牙周炎可以根据牙周组织病理中的局部基因表达来识别。我们计划利用当代基因表达谱技术来研究慢性牙周炎和侵袭性牙周炎在病理学上是否有足够的区别。将招募总共120名患者，60名慢性牙周炎患者和60名侵袭性牙周炎患者。将从每位患者中获取发炎牙龈组织样本，并使用微阵列分析局部基因表达模式。此外，牙周微生物群和全身抗体反应将分别通过棋盘DNA-DNA杂交和棋盘免疫印迹的方式针对20种细菌进行表征。本申请的第一个目的是检测慢性和侵袭性牙周炎患者的炎症牙周组织中的差异基因表达。这项分析将阐明目前公认的诊断分类是否有坚实的分子基础。第二个目的是探索一种新的分类方案的基础上的相似性基因表达的签名，并验证它对相关的临床，微生物和牙周炎的血清学标志物。最终，基于病理生物学的牙周炎分类将有助于正确诊断和有针对性的，有效的治疗预防和干预策略。

DESCRIPTION: The long-term goal of this research project is to facilitate the appropriate diagnosis and, ultimately, the successful treatment of patients with periodontal disease. Although specific bacteria of the Dental plaque biofilm are considered to be causative of periodontitis, it is the host's variable immuno-inflammatory response to the bacterial challenge that is largely recognized as the key determinant of the type, the extent and the severity of the disease. This response is thought to have a strong genetic component. Currently, the differential diagnosis of the major forms of periodontitis (chronic and aggressive) is primarily based on clinical signs after consideration of medical and oral health history. Nevertheless, the clinical presentation of both types of disease may be quite similar, and the response of both to standard therapeutic procedures may vary considerably. Importantly, a biologic basis for the distinction between chronic and aggressive periodontitis has not been well documented. The proposed project is based on the hypothesis that distinct forms of periodontitis can be identified based on local gene expression in pathological periodontal tissues. We plan to take advantage of contemporary gene expression profiling technology to investigate whether chronic and aggressive periodontitis are sufficiently distinct with respect to their pathobiology. A total of 120 patients, 60 with chronic and 60 with aggressive periodontitis will be recruited. Samples of inflamed gingival tissue will be obtained from each patient and will be analyzed with respect to local patterns of gene expression using microarrays. In addition, periodontal microbiota and systemic antibody responses will be characterized with respect to 20 bacterial species by means of checkerboard DNA-DNA hybridizations and checkerboard immunoblotting, respectively. The first Aim of this application is to examine the differential gene expression in inflamed periodontal tissues of patients with chronic and aggressive periodontitis. This analysis will elucidate whether the currently accepted diagnostic classification has a solid molecular basis. The second Aim is to explore a novel classification scheme based on similarities in gene expression signatures, and validate it against relevant clinical, microbiological and serological markers of periodontitis. Ultimately, a pathobiology-based classification of periodontitis will facilitate correct diagnosis and targeted, efficient therapeutic prevention and intervention strategies.