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

该项目解决了人类牙周韧带（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。在PDL细胞中检测到关键的免疫调节成分，并认为在牙周炎中具有一定的重要性。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。甲状旁腺素对骨代谢的影响与T细胞有关，因为T细胞反过来使基质细胞对甲状旁腺素敏感。我们将以HMGB1、RAGE、TLR-4、CD40、Wnt10b、OPG和RANKL为目标参数，对不同年龄供者的PDL细胞、巨噬细胞和T细胞进行单培养，研究PDL细胞对间歇性PTH的反应。共培养实验将检验PDL细胞在不同条件下对免疫细胞趋化和分化的影响。免疫功能低下和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，有助于它们的调节，并揭示免疫细胞在PTH对骨重塑的中介作用，反过来，澄清免疫过程是否可以被PTH修饰。

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.