Gene Expression in Chronic and Aggressive Periodontitis

慢性和侵袭性牙周炎的基因表达

• 批准号: 7094245
• 负责人: PANOS N PAPAPANOU
• 金额: $ 57.07万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7094245
• 关键词: biomarker; chronic disease /disorder; clinical research; dental disorder diagnosis; disease /disorder classification; disease /disorder etiology; gene expression; gene expression profiling; gingiva; human genetic material tag; human subject; microarray technology; patient oriented research; periodontitis

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.

描述：这项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，牙周炎的主要形式(慢性和侵袭性)的鉴别诊断主要是基于临床症状，然后考虑病史和口腔健康史。然而，这两种疾病的临床表现可能非常相似，对标准治疗程序的反应可能会有很大不同。重要的是，区分慢性牙周炎和侵袭性牙周炎的生物学基础还没有得到很好的记录。 拟议的项目是基于这样一个假设，即可以根据病理性牙周组织中的局部基因表达来识别不同形式的牙周炎。我们计划利用当代的基因表达谱技术来调查慢性牙周炎和侵袭性牙周炎在病理生物学方面是否有足够的区别。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被招募。发炎的牙龈组织样本将从每个患者身上获得，并将使用微阵列分析局部基因表达模式。此外，将分别通过棋盘DNA-DNA杂交法和棋盘免疫印迹法对20种细菌的牙周微生物区系和系统抗体反应进行表征。这项应用的第一个目的是检测慢性侵袭性牙周炎患者炎症牙周组织中的差异基因表达。这项分析将阐明目前被接受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基于基因表达特征相似性的分类方案，并与牙周炎的相关临床、微生物学和血清学标志物进行验证。最终，基于病理生物学的牙周炎分类将有助于正确的诊断和有针对性的、有效的治疗性预防和干预策略。

项目成果

Cell Type-Specific Decomposition of Gingival Tissue Transcriptomes.

牙龈组织转录组的细胞类型特异性分解。

• DOI: 10.1177/0022034520979614
• 发表时间: 2021
• 期刊: Journal of dental research
• 影响因子: 7.6
• 作者: Momen-Heravi,F;Friedman,RA;Albeshri,S;Sawle,A;Kebschull,M;Kuhn,A;Papapanou,PN
• 通讯作者: Papapanou,PN

Exploring Genome-Wide Expression Profiles Using Machine Learning Techniques.

使用机器学习技术探索全基因组表达谱。

• DOI: 10.1007/978-1-4939-6685-1_20
• 发表时间: 2017
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Kebschull,Moritz;Papapanou,PanosN
• 通讯作者: Papapanou,PanosN

Mini but mighty: microRNAs in the pathobiology of periodontal disease.

• DOI: 10.1111/prd.12095
• 发表时间: 2015-10
• 期刊: Periodontology 2000
• 影响因子: 18.6
• 作者: Kebschull M;Papapanou PN
• 通讯作者: Papapanou PN

Genome-Wide Analysis of Periodontal and Peri-Implant Cells and Tissues.

牙周和种植体周围细胞和组织的全基因组分析。

• DOI: 10.1007/978-1-4939-6685-1_18
• 发表时间: 2017
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Kebschull,Moritz;Hülsmann,Claudia;Hoffmann,Per;Papapanou,PanosN
• 通讯作者: Papapanou,PanosN

Granulocyte chemotactic protein 2 (gcp-2/cxcl6) complements interleukin-8 in periodontal disease.

• DOI: 10.1111/j.1600-0765.2008.01134.x
• 发表时间: 2009-08
• 期刊: Journal of periodontal research
• 影响因子: 3.5
• 作者: Kebschull M;Demmer R;Behle JH;Pollreisz A;Heidemann J;Belusko PB;Celenti R;Pavlidis P;Papapanou PN
• 通讯作者: Papapanou PN