Mechanical Compression by Simulating Orthodontic Tooth Movement in an In Vitro Model Modulates Phosphorylation of AKT and MAPKs via TLR4 in Human Periodontal Ligament Cells

• Published in: International journal of molecular sciences Vol. 23; no. 15; p. 8062
• Main Authors: Roth, Charlotte E., Craveiro, Rogerio B., Niederau, Christian, Malyaran, Hanna, Neuss, Sabine, Jankowski, Joachim, Wolf, Michael
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 22.07.2022; MDPI
• Subjects: AKT; AKT protein; Blocking antibodies; Cell signaling; Compression; compression force; Cytokines; Extracellular matrix; Fibroblasts; Human motion; human PDL; Inflammation; Investigations; Kinases; Ligaments; Lipids; MAPKs; Mechanical stimuli; Mediators; Molecular structure; Monoclonal antibodies; monoclonal antibody TLR4; NF-κB protein; Orthodontics; Pattern recognition; Periodontal ligament; Periodontium; Phosphorylation; Proteins; Signal transduction; Stem cells; sterile inflammation; Teeth; TLR4 protein; Toll-like receptors; Vascular endothelial growth factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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/cm2, 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.