Interplay of human periodontal ligament cells and immune cells - age-dependent aspects of the cellular response to intermittent PTH

人牙周膜细胞和免疫细胞的相互作用——对间歇性 PTH 的细胞反应的年龄依赖性方面

• 批准号: 81897061
• 负责人: Privatdozent Dr. Stefan Lossdörfer
• 金额: --
• 依托单位: Zentrum für Zahn-, Mund- und Kieferheilkunde
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/81897061?language=en
• 关键词: Interplay; human; periodontal; ligament; cells

This project addresses age-dependent aspects of the immune regulatory function of human periodontal ligament (PDL) cells with special attention directed to the role of an inflammatory microenvironment. Crucial immune regulatory components have been detected in PDL cells and attributed a certain importance in periodontitis. PDL cells have been identified as target cells for regenerative strategies, in part due to their anabolic response to an intermittent parathyroid hormone (PTH) stimulation. The PTH effect on bone metabolism has been linked to T cells since those in turn sensitize stromal cells to PTH. The PDL cell response to intermittent PTH will be investigated in monocultures of PDL cells from donors of different age, macrophages, and T cells with HMGB1, RAGE, TLR-4, CD40, Wnt10b, OPG, and RANKL as target parameters. Coculture experiments will examine the influence of PDL cells on immune cell chemotaxis and differentiation under variable conditions. Immunocompromised and TLR-4 knockout mice will serve to analyze the physiological relevance. These experimental approaches will elucidate how PDL cells are influenced by immunologic processes or, vice versa, contribute to their regulation, and disclose the role of immune cells for the mediation of the PTH effect on bone remodeling and, conversely, clarify whether immunologic processes can be modified by PTH.

该项目致力于人类牙周膜（PDL）细胞免疫调节功能的年龄依赖性方面，特别关注炎症微环境的作用。牙周膜细胞中存在重要的免疫调节成分，在牙周炎的发生发展中起着重要作用。PDL细胞已被确定为再生策略的靶细胞，部分原因是它们对间歇性甲状旁腺激素（PTH）刺激的合成代谢反应。PTH对骨代谢的影响与T细胞有关，因为T细胞反过来使基质细胞对PTH敏感。将在来自不同年龄供体的PDL细胞、巨噬细胞和T细胞的单一培养物中研究PDL细胞对间歇性PTH的反应，并将HMGB 1、TNF α、TLR-4、CD 40、Wnt 10 b、OPG和RANKL作为目标参数。共培养实验将检查PDL细胞在可变条件下对免疫细胞趋化性和分化的影响。免疫受损和TLR-4敲除小鼠将用于分析生理相关性。这些实验方法将阐明PDL细胞如何受到免疫过程的影响，反之亦然，有助于其调节，并揭示免疫细胞对PTH对骨重塑作用的介导作用，反之亦然，阐明免疫过程是否可以通过PTH进行修饰。