Department of Orthodontics, Dental Clinic, University of Aachen, 52074 Aachen, Germany.
Helmholtz Institute for Biomedical Engineering, BioInterface Group, RWTH Aachen University, 52056 Aachen, Germany.
Int J Mol Sci. 2022 Jul 22;23(15):8062. doi: 10.3390/ijms23158062.
Mechanical compression simulating orthodontic tooth movement in in vitro models induces pro-inflammatory cytokine expression in periodontal ligament (PDL) cells. Our previous work shows that TLR4 is involved in this process. Here, primary PDL cells are isolated and characterized to better understand the cell signaling downstream of key molecules involved in the process of sterile inflammation via TLR4. The TLR4 monoclonal blocking antibody significantly reverses the upregulation of phospho-AKT, caused by compressive force, to levels comparable to controls by inhibition of TLR4. Phospho-ERK and phospho-p38 are also modulated in the short term via TLR4. Additionally, moderate compressive forces of 2 g/cm, a gold standard for static compressive mechanical stimulation, are not able to induce translocation of Nf-kB and phospho-ERK into the nucleus. Accordingly, we demonstrated for the first time that TLR4 is also one of the triggers for signal transduction under compressive force. The TLR4, one of the pattern recognition receptors, is involved through its specific molecular structures on damaged cells during mechanical stress. Our findings provide the basis for further research on TLR4 in the modulation of sterile inflammation during orthodontic therapy and periodontal remodeling.
机械压迫模拟正畸牙齿移动在体外模型中诱导牙周膜（PDL）细胞中促炎细胞因子的表达。我们之前的工作表明 TLR4 参与了这一过程。在这里，分离和表征原代牙周膜细胞，以更好地了解通过 TLR4 参与无菌炎症过程的关键分子下游的细胞信号转导。TLR4 单克隆阻断抗体通过抑制 TLR4，显著逆转了由压缩力引起的磷酸化 AKT 的上调，使其水平与对照相当。TLR4 还在短期内调节磷酸化 ERK 和磷酸化 p38。此外，2 g/cm 的适度压缩力（静态压缩机械刺激的金标准）不能诱导 NF-kB 和磷酸化 ERK 向核内易位。因此，我们首次证明 TLR4 也是在压力下信号转导的触发因素之一。TLR4 作为模式识别受体之一，通过其在机械应激过程中受损细胞上的特定分子结构参与其中。我们的发现为进一步研究 TLR4 在正畸治疗和牙周重塑过程中无菌炎症的调节奠定了基础。
