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

这个项目致力于人类牙周膜(PDL)细胞免疫调节功能的年龄相关方面，特别关注炎症微环境的作用。已在牙周膜细胞中检测到关键的免疫调节成分，并认为其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目标细胞，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。以HMGB1、RAGE、TLR-4、CD40、WNT10b、OPG和RANKL为靶标，研究不同年龄供者、巨噬细胞和T细胞的PDL细胞对间歇性甲状旁腺素的反应。共培养实验将检测在不同条件下PDL细胞对免疫细胞趋化和分化的影响。免疫缺陷和TLR-4基因敲除小鼠将用于分析其生理相关性。这些实验方法将阐明免疫过程如何影响PDL细胞，反之亦然，并揭示免疫细胞在甲状旁腺素在骨重建中的中介作用，反之，阐明甲状旁腺素是否可以改变免疫过程。

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.