OBJECTIVE Biomechanical orthodontics loading of the periodontium initiates a cascade of inflammatory signaling events that induce periodontal remodeling and finally facilitate orthodontic tooth movement. Pattern recognition receptors such as toll-like receptors (TLRs) have been well characterized for their ability to induce the activation of inflammatory, immunomodulatory cytokines. Here, we examined whether the cellular response of human periodontal ligament (hPDL) cells to mechanical stress involves TLR-4 signaling in vitro. MATERIALS AND METHODS Confluent hPDL cells were cultured in the presence of 5 μg/ml TLR-4 antibody (TLR-4ab) for 1 h prior to the induction of compressive forces by the use of round glass plates for 24 h. At harvest, interleukin-6 and interleukin-8 (IL-6, IL-8) mRNA and protein expression were analyzed by real-time PCR and ELISA. The immunomodulatory role of mechanical cell stress and TLR-4 signaling was addressed in co-culture experiments of hPDL and THP-1 cells targeting monocyte adhesion and by culturing osteoclastic precursors (RAW 264.7) in the presence of the conditioned medium of hPDL cells that had been mechanically loaded before. RESULTS Basal expression of IL-6 and IL-8 was not affected by TLR-4ab, but increased significantly upon mechanical loading of hPDL cells. When cells were mechanically stressed in the presence of TLR-4ab, the effect seen for loading alone was markedly reduced. Likewise, monocyte adhesion and osteoclastic differentiation were enhanced significantly by mechanical stress of hPDL cells and this effect was partially inhibited by TLR-4ab. CONCLUSIONS The results of the present study indicate a proinflammatory and immunomodulatory influence of mechanical loading on hPDL cells. Intracellular signaling involves a TLR-4-dependent pathway. CLINICAL RELEVANCE These findings hold out the prospect of interfering with the cellular response to mechanical cell stress in order to minimize undesired side effects of orthodontic tooth movement.

中文翻译：

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正畸细胞应激可通过人体内TLR-4信号传导调节人PDL细胞中促炎细胞因子的表达并诱导免疫调节作用。

目的牙周组织的生物力学正畸加载可引发一系列炎症信号，从而引起牙周重塑并最终促进正畸牙齿移动。模式识别受体，例如toll样受体（TLR），已被很好地表征，具有诱导炎症性免疫调节细胞因子激活的能力。在这里，我们检查了人类牙周膜（hPDL）细胞对机械应力的细胞反应是否涉及体外TLR-4信号传导。材料与方法将融合的hPDL细胞在5μg/ ml TLR-4抗体（TLR-4ab）存在下培养1 h，然后通过使用圆形玻璃板诱导压缩力24 h。收获时，白介素6和白介素8（IL-6，通过实时PCR和ELISA分析IL-8）mRNA和蛋白质表达。在针对单核细胞粘附的hPDL和THP-1细胞的共培养实验中，以及在具有以下条件的hPDL细胞条件培养基的存在下培养破骨细胞前体（RAW 264.7），可以解决机械细胞应激和TLR-4信号传导的免疫调节作用：之前已经过机械加载。结果IL-6和IL-8的基础表达不受TLR-4ab的影响，但在机械加载hPDL细胞后显着增加。当在TLR-4ab存在的情况下对细胞进行机械应力处理时，单独加载所见的效果明显降低。同样，hPDL细胞的机械应力显着增强了单核细胞粘附和破骨细胞分化，并且这种作用被TLR-4ab部分抑制。结论本研究结果表明机械负荷对hPDL细胞具有促炎和免疫调节作用。细胞内信号转导涉及TLR-4依赖性途径。临床相关性这些发现提供了干扰细胞对机械性细胞应力的反应的前景，从而最大程度地减少了正畸牙齿运动的不良副作用。