Human Periodontal Ligament Fibroblasts (hPDLF), as part of the periodontal apparatus, modulate inflammation, regeneration and bone remodeling. Interferences are clinically manifested as attachment loss, tooth loosening and root resorption. During orthodontic tooth movement (OTM), remodeling and adaptation of the periodontium is required in order to enable tooth movement. hPDLF involvement in the early phase-OTM compression side was investigated for a 72-h period through a well-studied in vitro model. Changes in the morphology, cell proliferation and cell death were analyzed. Specific markers of the cell cycle were investigated by RT-qPCR and Western blot. The study showed that the morphology of hPDLF changes towards more unstructured, unsorted filaments under mechanical compression. The total cell numbers were significantly reduced with a higher cell death rate over the whole observation period. hPDLF started to recover to pretreatment conditions after 48 h. Furthermore, key molecules involved in the cell cycle were significantly reduced under compressive force at the gene expression and protein levels. These findings revealed important information for a better understanding of the preservation and remodeling processes within the periodontium through Periodontal Ligament Fibroblasts during orthodontic tooth movement. OTM initially decelerates the hPDLF cell cycle and proliferation. After adapting to environmental changes, human Periodontal Ligament Fibroblasts can regain homeostasis of the periodontium, affecting its reorganization.

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.

Summary: Background: Orthodontic therapy aims to treat misaligned teeth and jaws to improve dental occlusion as well as the function and aesthetics of the masticatory system. Continuous data collection to check treatment quality is of great importance for the constant optimization of orthodontic care. Objective: The aim of this retrospective multicentre cohort study was to systematically determine the outcome and quality of orthodontic treatment by applying the internationally established Index of Orthodontic Treatment Need (IOTN) and Peer Assessment Rating (PAR) index in multiple clinical settings for a representative number of patient cases. Materials and methods: A total of 1509 consecutive orthodontic patient cases (treatment completion between January 2018 and December 2020) from three representative orthodontic centres (University clinic, city office, small town office) were analysed in a multicentre study. The pre- and post-treatment casts were scanned, digitally measured, and partially automatically evaluated using the IOTN and PAR indices. Results: A statistically significant improvement in occlusion was observed for medically necessary treatment of IOTN grades 4 and 5 in 97.30 per cent of the analysed cases and for treatment-requiring grades 2 and 3 in 94.08 per cent of the analysed cases. The average percentage PAR improvement was 76.51 per cent. 72.50 per cent of cases showed improvement of more than 70 per cent. The mean PAR index score was reduced from 28.19 ± 9.49 to 6.22 ± 5.41 points. Conclusion: The present data demonstrate that orthodontic treatment is efficient in inducing significant improvement of malocclusions in general and has a high success rate with severe dysgnathia.

Periodontal defects’ localization affects wound healing and bone remodeling, with faster healing in the upper jaw compared to the lower jaw. While differences in blood supply, innervation, and odontogenesis contribute, cell-intrinsic variances may exist. Few studies explored cell signaling in periodontal ligament stem cells (PDLSC), overlooking mandible-maxilla disparitiesUsing kinomics technology, we investigated molecular variances in PDLSC. Characterization involved stem cell surface markers, proliferation, and differentiation capacities. Kinase activity was analyzed via multiplex kinase profiling, mapping differential activity in known gene regulatory networks. Upstream kinase analysis identified stronger EphA receptor expression in the mandible, potentially inhibiting osteogenic differentiation. The PI3K-Akt pathway showed higher activity in lower-jaw PDLSC. PDLSC from the upper jaw exhibit superior proliferation and differentiation capabilities. Differential activation of gene regulatory pathways in upper vs. lower-jaw PDLSC suggests implications for regenerative therapies.

The cellular and molecular mechanisms of orthodontic tooth movement (OTM) are not yet fully understood, partly due to the lack of dynamical datasets within the same subject. Inflammation and calcification are two main processes during OTM. Given the high sensitivity and specificity of [⁶⁸Ga]Ga-Pentixafor and Sodium [¹⁸F]Fluoride (Na[¹⁸F]F) for inflammation and calcification, respectively, the aim of this study is to assess their ability to identify and monitor the dynamics of OTM in an established mouse model. To monitor the processes during OTM in real time, animals were scanned using a small animal PET/CT during week 1, 3, and 5 post-implantation, with [⁶⁸Ga]Ga-Pentixafor and Na[¹⁸F]F. Both tracers showed an increased uptake in the region of interest compared to the control. For [⁶⁸Ga]Ga-Pentixafor, an increased uptake was observed within the 5-week trial, suggesting the continuous presence of inflammatory markers. Na[¹⁸F]F showed an increased uptake during the trial, indicating an intensification of bone remodelling. Interim and end-of-experiment histological assessments visualised increased amounts of chemokine receptor CXCR4 and TRAP-positive cells in the periodontal ligament on the compression side. This approach establishes the first in vivo model for periodontal remodelling during OTM, which efficiently detects and monitors the intricate dynamics of periodontal ligament.

Objective: Resveratrol is a plant polyphenol known for its anti-inflammatory and pro-regenerative properties. These could be beneficial in controlling potential side effects of orthodontic treatment, such as apical root resorption. Orthodontic tooth movement occurs as part of a sterile inflammatory response. However, dysregulation of this process can result in pathologically increased osteoclast activity in the radicular vicinity, leading to unwanted root resorption. Previous studies have shown that root cementum cells can modulate recruitment of osteoclast precursors and cementum repair. Material and methods: We investigated the effect of resveratrol on mechanically stimulated murine cementoblasts (OCCM-30) with regards to cell viability, and mRNA expression and protein levels of pro-inflammatory cytokines. Furthermore, the modulation of central related kinases was investigated. Results: Resveratrol increased viability of OCCM-30 in a time- and dose-dependent manner and significantly reduced upregulation of pERK and pAKT, upstream regulators of key cellular metabolic pathways. Furthermore, we describe for the first time that cementoblasts respond to compression with accelerated activation of STAT3 and increased translocation of NF-κB p65 into the nucleus. Conclusion: This study shows a regulation of pAKT and pERK by resveratrol in OCCM-30 cells without a negative effect on cell viability. Therefore, resveratrol may have the potential to modulate the periodontal response to mechanical stimulation.