The diversified research on. the genes related periodontal disease

多元化的研究。

• 批准号: 10357020
• 负责人: KURIHARA Hidemi
• 金额: $ 16.19万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10357020/
• 关键词: genetic diagnosis; Porphyromonas gingivalis; IL-1; autoantibody; HLA class II; cytolethal distending toxin; hypophosphatasia; CDR3; Porphyromonas gingivalis; 低フォスファターゼ症; 歯周病; 遺伝子; 発症; 歯周病感受性; 歯周病関連菌

In this project, we evaluate the genes related periodontal disease from the diversified aspects, infected bacteria, host defense system, tissue metabolism, and tissue regeneration. Analysis of DNA sequence of hemagglutinin from Porphyromonas gingivalis revealed its functional domain. The binding domain contains the specific sequence, PVQNT, similar to influenza virus. A novel gene (Aa cdt) encoding cytolethal distending toxin (CDT) was successfully cloned from Actinobacillus actinomycetemcomitans. Aa cdt was composed with three clusters, and each cluster was encoding CDT-A, -B, and -C. CDT-A, -B and -C were essential for expressing CDT activity.The genes related autoantibody production in patients with periodontitis were evaluated on T cell receptor (TCR) and human leukocyte antigen (HLA). The peripheral T cells were stimulated by hrHSP60 or P. gingivalis GroEL and DNA sequence of CDR3 region of their TCR β-chain. The amino-acid sequenee of CDR3 was the same between the expanded T cell … More clone and the accumulated T cell clone in inflamed gingival tissue. The HLA class II genotypes of patients with periodontitis, autoantibody production and PVB 19 infection were analyzed by PCR-RFLP. The frequencies of DQA1 *0101, DQA1 *0501, and DQB1*0503 in patients with periodontitis, autoantibody production and PVB 19 infection were higher than in other patients and healthy subjects. The relationship between IL-1 genotypes and prevalence of adult periodontitis was reported in the United State, however we could not found this relationship in Japanese.Two patients with hypophosphatasia, usually accompanied with periodontitis, and their family members were analyzed to detect mutation on tissue-nonspecifie alkaline phosphatase gene. Novel three point mutations on the alkaline phosphatase gene were revealedNovel genes related periodontal tissue regeneration were found by the subtraction method between wound periodontal tissue under tissue repair and healthy periodontal tissue. Sixteen novel cDNAS in enhanced expression genes and 9 novel cDNAS in depressed expression genes were successfully cloned. Less

本课题将从感染细菌、宿主防御系统、组织代谢、组织再生等多个方面对牙周病相关基因进行评价。对牙龈卟啉单胞菌血凝素的DNA序列分析揭示了其功能域。结合域包含与流感病毒相似的特异性序列PVQNT。从放线菌comitans中成功克隆了一个编码细胞致死膨胀毒素（cdt）的新基因Aa cdt。Aa cdt由3个簇组成，每个簇分别编码cdt - a、-B和-C。CDT- a、-B和-C是表达CDT活性所必需的。采用T细胞受体（TCR）和人白细胞抗原（HLA）检测牙周炎患者自身抗体产生相关基因。用hrHSP60或牙龈P. GroEL及其TCR β链CDR3区DNA序列刺激外周T细胞。CDR3的氨基酸序列在炎症牙龈组织扩增的T细胞克隆和积累的T细胞克隆之间是相同的。采用PCR-RFLP方法分析牙周炎患者HLAⅱ类基因型、自身抗体产生及PVB - 19感染情况。牙周炎、自身抗体产生和PVB 19感染患者DQA1 *0101、DQA1 *0501、DQB1*0503的频率高于其他患者和健康人群。IL-1基因型与成人牙周炎患病率之间的关系在美国有报道，但在日本没有发现这种关系。对2例常伴有牙周炎的低磷酸酶患者及其家族成员进行组织非特异性碱性磷酸酶基因突变检测。通过组织修复损伤后的牙周组织与健康牙周组织之间的差值法，发现了新的与牙周组织再生相关的基因。成功克隆了16个表达增强基因的新cdna和9个表达抑制基因的新cdna。少

项目成果

Okada,M.,et al.: "Genetic,Immunological and Microbiological Study of Family Members Manifesting Early-Onset Periodontitis" J.Dent.Res.78. 513-513 (1999)

Okada,M.,et al.：“表现早发性牙周炎的家庭成员的遗传、免疫学和微生物学研究”J.Dent.Res.78。

Watanabe, H, et al.: "Molecular diagnosis of hypophosphatasia with severe periodontitis."J. Periodontol.. 70. 688-691 (1999)

Watanabe, H, et al.：“低磷酸酯酶症伴严重牙周炎的分子诊断”。

Nakajima T.et al.: "Detection of clonotypic changes of T cells after stimulation with Porphyromonas gingivalis" Oral Microbiology and Immunology. 13. 238-245 (1998)

Nakajima T.et al.：“牙龈卟啉单胞菌刺激后 T 细胞克隆型变化的检测”口腔微生物学和免疫学。

Kataoka, M. et al.: "Cyclosporin A decreases the degradation of type I collagen in rat gingival overgrowth."J. Cell. Physiol.. (in press).

Kataoka, M. 等人：“环孢素 A 可以减少大鼠牙龈过度生长中 I 型胶原蛋白的降解。”J.

Yoshino,H: "Autoantibody agaist gingival fibroblast antigen in serum from patients with periodontitis"J.Dent.Res.. 77. 648-648 (1998)

Yoshino,H：“牙周炎患者血清中抗牙龈成纤维细胞抗原的自身抗体”J.Dent.Res.. 77. 648-648 (1998)