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.

该项目介绍了人类牙周韧带（PDL）细胞免疫调节功能的年龄依赖性方面，并特别注意炎症性微环境的作用。在PDL细胞中已检测到关键的免疫调节成分，并归因于牙周炎至关重要。 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对骨代谢的作用已与T细胞联系起来，因为这些作用又使基质细胞敏感到PTH。 PDL细胞对间歇性PTH的反应将在不同年龄，巨噬细胞和T细胞的PDL细胞的单一培养物中进行研究，其HMGB1，RAGE，RAGE，TLR-4，CD40，CD40，WNT10B，OPG和RANKL作为目标参数。共培养实验将检查PDL细胞对可变条件下免疫细胞趋化性和分化的影响。免疫功能低下和TLR-4敲除小鼠将有助于分析生理相关性。这些实验方法将阐明PDL细胞如何受到免疫学过程的影响，反之亦然，有助于其调节，并披露免疫细胞在PTH效应中介导PTH对骨重塑的作用，并相反地阐明了免疫学过程是否可以通过PTH修改。