Apart from periodontal ligament fibroblasts, immune cells like macrophages also play an important mediating role in orthodontic tooth movement (OTM). Upon orthodontic force application to malpositioned teeth, macrophages in the periodontal ligament get exposed to both mechanical strain and hypoxic conditions (via a compression of blood vessels). In this study, we assessed the relative impact of orthodontically induced mechanical strain and hypoxic conditions on macrophages for the mediation and regulation of OTM. Macrophages were stimulated with physiological orthodontic compressive forces of 2 g/cm² for 4 h and 24 h on gas-impermeable or gas-permeable cell culture plates under normoxic or hypoxic cell culture conditions. We quantified expression of genes involved in inflammation (Tnf, Il-6, and Cox-2), extracellular remodelling (Mmp-9), and angiogenesis (Vegf) by RT-qPCR. Furthermore, we analysed HIF-1α, prostaglandin-E2, and VEGF protein expression via immunoblotting or ELISA. Mechanical strain and oxygen supply both differentially affected expression of genes and proteins involved in inflammation and angiogenesis. In this context, we found that HIF-1α protein levels were elevated by combined mechanical strain and hypoxic conditions, whereas gas-permeable plates providing sufficient oxygen supply prevented HIF-1α stabilization at the protein level after pressure application on macrophages. Our results thus indicate that macrophages involved in the mediation of OTM are affected by and respond differently to hypoxic conditions and mechanical compressive strain, which occur concomitantly during OTM, than periodontal ligament fibroblasts (PDLF), thus indicating different roles of these cells in the regulation of OTM at the cellular-molecular level. We further observed that contrary to PDLF HIF-1α stabilization in macrophages is rather induced via the decreased oxygen supply associated with OTM than via mechanotransduction by mechanical strain.

中文翻译：

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模拟正畸牙齿运动模型中巨噬细胞供氧的作用。

除牙周膜成纤维细胞外，免疫细胞（如巨噬细胞）在正畸牙齿移动（OTM）中也起着重要的中介作用。在畸形牙齿上施加正畸力后，牙周膜中的巨噬细胞会暴露于机械应变和低氧状态（通过压缩血管）。在这项研究中，我们评估了正畸诱发的机械应变和低氧条件对巨噬细胞介导和调节OTM的相对影响。在常氧或低氧细胞培养条件下，在不透气或透气的细胞培养板上分别以2 g / cm ^2的生理正畸压缩力刺激巨噬细胞4 h和24 h。我们量化了与炎症有关的基因的表达（Tnf，II-6和Cox-2），细胞外重塑（Mmp-9）和血管生成（Vegf）。此外，我们通过免疫印迹或ELISA分析了HIF- 1α，前列腺素-E2和VEGF蛋白的表达。机械应变和氧气供应均差异地影响涉及炎症和血管生成的基因和蛋白质的表达。在这种情况下，我们发现机械应力和低氧条件共同作用会提高HIF- 1α的蛋白水平，而提供足够氧气的透气板阻止了HIF- 1α在巨噬细胞上施加压力后，蛋白质水平稳定。因此，我们的结果表明，参与OTM介导的巨噬细胞受牙周膜缺氧成纤维细胞（PDLF）的影响，并且对低氧条件和机械压迫应变的影响不同，并且对它们的反应不同，这表明这些细胞在调节过程中的作用不同OTM在细胞分子水平上的表达。我们进一步观察到，与PDLF HIF- 1α稳定相反，巨噬细胞是通过与OTM相关的氧气供应减少而不是通过机械应变进行机械转导来诱导稳定的。