Christian Niederau

Background: Increasing clinical and experimental evidence suggests that the upper and lower jaw exhibit pronounced functional and structural disparities that cannot be explained solely by classical anatomical differences. A central, yet unresolved question is whether periodontal ligament stem cells (PDLSCs) from these distinct regions display site-specific molecular signaling patterns in response to mechanical stress. We propose that PDLSCs derived from maxillary and mandibular regions activate distinct kinase signaling networks upon mechanical stimulation, thereby establishing a jaw-specific mechanobiological fingerprint. Methods: PDLSCs were isolated from seven healthy donor teeth and exposed to a static compressive force of 2 g/cm ² . Kinase activity was profiled using a high-throughput PamChip ^® peptide arrays that target both protein tyrosine kinases (PTKs) and serine/threonine kinases (STKs). Downstream pathway enrichment analyses were conducted using the Wikipathways, Gene Ontology (GO), KEGG, and Enriched pathways databases. Results: Mechanical stimulation induced distinct kinase activation signatures depending on jaw origin. Maxillary PDLSCs displayed a predominance of STK activation, while mandibular cells showed a relative reduction in PTK signaling. Only two PTKs and four STKs were consistently regulated across both regions, supporting the presence of a region-specific mechanotransduction profile. Conclusion: These findings support our hypothesis that localized differences in kinase signaling may constitute a molecular basis for the clinically observed jaw-specific phenomena, such as heterogeneous orthodontic tooth movement and alveolar bone remodeling. Jaw-dependent mechanotransduction pathways can therefore be considered key determinants of periodontal biology and may provide a basis for follow-up studies aimed at enabling the development of personalized orthodontic and regenerative strategies.

Objectives: The digitalization of numerous dental workflows has significantly expanded the possibilities of digital treatment planning in recent years. By using additively manufactured templates and guides, preoperative planning can be realized reliably and minimally invasively on the patient. However, these devices may break under mechanical stress during use, so that fragments may remain in the surgical field, be swallowed or aspirated. This study investigates the radiologic detectability of additively manufactured materials in surrounding soft tissue. Methods: The visual detectability of standardized scan bodies and splinters of 15 different materials used in dentistry was analyzed using cone-beam computed tomography (CBCT). Porcine muscle and subcutaneous tissue were used as surrounding structures. In addition, computed tomography (CT) was used to measure the radiation densities of the materials in Hounsfield units to obtain quantitative reference values for the recognizability of the materials in comparison with soft tissues. Results: The radiodensities in CT images of all modern materials used in computer-aided manufacturing ranged from 68.94 ± 5.32 HU to 130.47 ± 4.52 HU and were thus very similar to those of muscle tissue. In CBCT images, large cylinders as well as small splinters of these materials were hardly visible in both subcutaneous fat and muscular tissues. Overall, the small splinters were more difficult to differentiate from the surrounding tissue than the larger cylinders. The conventional dental materials Futar D ^® and Luxatemp ^® exhibited significantly higher radiopacity at 1031.18 ± 12.97 HU and 3243.96 ± 69.03 HU. Conclusion: The results of this study show that neither CT nor CBCT may currently not be suitable for visualising modern 3D-printed dental materials against surrounding soft tissue. This is due to the materials’ insufficient radiopacity, which prevents clear delineation. Classic materials for temporal direct restorations and silicones were much easier to detect than the tested additively manufactured materials.

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.

Background/Objectives: Initial sterile inflammation is an essential molecular process in the periodontium during orthodontic tooth movement. A better understanding and possible modulations of these processes are of great interest to develop individual therapies for special patient groups. The prenylated plant polyphenol xanthohumol (XN) could have modulating effects as it has shown anti-inflammatory and angiogenesis-inhibiting effects in various cell lines. This study investigated the anti-inflammatory properties of XN in an in vitro model of compressively stimulated human periodontal ligament stem cells (hPDLSCs), which have a different function in the periodontium than the previously used cementoblasts. Methods: The expression of inflammatory markers at the mRNA and protein levels and the regulation of central kinases were investigated. Results: XN showed a dose-dependent influence on cell viability. Low concentrations between 0.2 and 4 µM showed positive effects, while 8 µM caused a significant decrease in viability after 24 h. Mechanical stimulation induced an upregulation of pro-inflammatory gene (IL-6, COX2) and protein (IL-6) expression. Here, XN significantly reduced stimulation-related IL-6 mRNA and gene expression. Furthermore, the phosphorylation of AKT and ERK was upregulated by mechanical stimulation, and XN re-established phosphorylation at a level similar to the control. Conclusions: We demonstrated a selective anti-inflammatory effect of XN in hPDLSCs. These findings provide the basis for further investigation of XN in the modulation of inflammatory responses in orthodontic therapy and the treatment of periodontal inflammation.

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.

Objectives: Long-term stabilization of orthodontic treatment outcomes is an everyday challenge in orthodontics. The use of permanently attached lingual retainers has become gold standard. However, in some cases, patients with fixed lingual retainers show retainer-associated side effects. Aiming to reduce these side effects, clinical knowledge about how tooth and arch form stability adaption takes place over time is important to improve long-term retention protocols. Therefore, the present study aimed to investigate occlusion stability and risks for a newly developing malocclusion in a time-dependent manner in patients being treated with permanent 2‑point steel retainers. Materials and methods: In this retrospective cohort study, a total of 66 consecutive patients with round stainless-steel retainers were analyzed for postorthodontic occlusion changes after 1 year (group 1, n = 33) and 3 years (group 2, n = 33). Digital Standard Tessellation Language (STL) datasets of the lower jaw were obtained before retainer insertion (T0), and after a 1- (T1) or 3‑year (T2) retention period. Using superimposition software, T1 and T2 situations were compared to T0 regarding rotational and translational changes in tooth positions in all three dimensions. Results: Occlusion changes were low in both groups. The investigated lower canines were nearly stable in the 1‑ and 3‑year group, although a retention-time-dependent increase in tooth position change of the central and lateral incisors could be observed. Conclusion: The present data provide evidence for time-dependent development of posttherapeutic occlusal adaption limited to central and lateral incisors in patients treated with a 2-point retainer. The observed occlusal changes should be interpreted as an occlusal adaption process rather than severe posttreatment changes associated with the orthodontic retainer.

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.

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.

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.