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Animal experiments are essential for the elucidation of biological-cellular mechanisms in the context of orthodontic tooth movement (OTM). So far, however, no studies comparatively assess available mouse models regarding their suitability. OTM of first upper molars was induced in C57BL/6 mice either via an elastic band or a NiTi coil spring for three, seven or 12 days. We assessed appliance survival rate, OTM and periodontal bone loss (µCT), root resorptions, osteoclastogenesis (TRAP + area) and local expression of OTM-related genes (RT-qPCR). Seven days after the elastic bands were inserted, 87% were still in situ, but only 27% after 12 days. Survival rate for the NiTi coil springs was 100% throughout, but 8.9% of the animals did not survive. Both methods induced significant OTM, which was highest after 12 (NiTi spring) and 7 days (band), with a corresponding increase in local gene expression of OTM-related genes and osteoclastogenesis. Periodontal bone loss and root resorptions were not induced at a relevant extent by neither of the two procedures within the experimental periods. To induce reliable OTM in mice beyond 7 days, a NiTi coil spring is the method of choice. The elastic band method is recommended only for short-term yes/no-questions regarding OTM.

Different structures and cell types of the periodontium respond to orthodontic tooth movement (OTM) individually. Cementoblasts (OC/CM) located in the immediate vicinity of the fibroblasts on the cement have found way to the centre of actual research. Here, we identify and validate possible reference genes for OC/CM cells by RT-qPCR with and without static compressive loading. We investigated the suitability of 3 reference genes in an in vitro model of cementoblast cells using four different algorithms (Normfinder, geNorm, comparative delta-C t method and BestKeeper) under different confluences and time. Comparable to our previous publications about reference genes in OTM in rats and human periodontal ligament fibroblasts (hPDLF), Rpl22 in murine OC/CM cells appears as the least regulated gene so that it represents the most appropriate reference gene. Furthermore, unlike to the expression of our recommended reference genes, the expression of additionally investigated target genes changes with confluence and under loading compression. Based on our findings for future RT-qPCR analyses in OC/CM cells, Rpl22 or the combination Rpl22/Tbp should be favored as reference gene. According to our results, although many publications propose the use of Gapdh , it does not seem to be the most suitable approach.

Selection of appropriate housekeeping genes is essential for the validity of data normalization in reverse transcription quantitative PCR (RT-qPCR). Synovial fibroblasts (SF) play a mediating role in the development and progression of osteoarthritis (OA) pathogenesis, but there is no information on reliable housekeeping genes available. Therefore the goal of this study was to identify a set of reliable housekeeping genes suitable for studies of mechanical loading on SF from healthy and OA patients. Nine genes were evaluated towards expression stability and ranked according their relative stability determined by four different mathematical procedures (geNorm, NormFinder, BestKeeper and comparative ΔCq). We observed that RPLP0 (ribosomal protein, large, P0) and EEF1A1 (eukaryotic translation elongation factor 1 alpha 1) turned out to be the genes with the most stable expression in SF from non-OA or OA patients treated with or without mechanical loading. According to geNorm two genes are sufficient for normalization throughout. Expression of one tested target gene varied considerably, if normalized to different candidate housekeeping genes. Our study provides a tool for accurate and valid housekeeping gene selection in gene expression experiments on SF from healthy and OA patients with and without mechanical loading in consistent with the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines and additionally demonstrates the impact of proper housekeeping gene selection on the expression of the gene of interest.

To evaluate the shear bond strength (SBS) of different attachment materials used for lingual bonding, the influence of artificial aging and the radii of curvature of the enamel surface on SBS, 192 third molars were photographed to determine the radius of curvature of the oral surface. After phosphoric acid etching a cylindrical test piece was bonded to the oral enamel using a mold that was filled with a chemically curing (Maximum Cure, Transbond IDB Premix) or a dual-curing (Nexus NX3, RelyX Unicem2) attachment material. SBS was tested after 24 h, 500 thermal cycles or 90 days at 37 °C with a universal testing machine. Computed tomography scans were performed to determine the bonded surface and calculate SBS. Values ranged from 8.3 to 20.9 MPa. RelyX Unicem2 showed the highest SBS values at baseline, 500 thermal cycles and after 90 days ( p  < 0.001). Ninety days of wet storage significantly reduced SBS of Maximum Cure ( p  = 0.028). The radius of curvature correlated positively with SBS ( r s  = 0.204, p  = 0.005). The SBS of all attachment materials was sufficient for clinical use, even after artificial aging. RelyX Unicem2 showed almost twice as high SBS values as the other attachment materials.

Objectives The aims of this study were to investigate the antimicrobial efficacy of antiseptics in saliva-derived microcosm biofilms, and to examine phenotypic adaption of bacteria upon repeated exposure to sub-inhibitory antiseptic concentrations. Methods Saliva-derived biofilms were formed mimicking caries- or gingivitis-associated conditions, respectively. Microbial compositions were analyzed by semiconductor-based 16S rRNA sequencing. Biofilms were treated with CHX, CPC, BAC, ALX, and DQC for 1 or 10 min, and colony forming units (CFU) were evaluated. Phenotypic adaptation of six selected bacterial reference strains toward CHX, CPC, and BAC was assessed by measuring minimum inhibitory concentrations (MICs) over 10 passages of sub-inhibitory exposure. Protein expression profiles were investigated by SDS-PAGE. Results Both biofilms showed outgrowth of streptococci and Veillonella spp., while gingivitis biofilms also showed increased relative abundances of Actinomyces , Granulicatella , and Gemella spp. Antiseptic treatment for 1 min led to no relevant CFU-reductions despite for CPC. When treated for 10 min, CPC was most effective followed by BAC, ALX, CHX, and DQC. Stable adaptations with up to fourfold MIC increases were found in E. coli toward all tested antiseptics, in E. faecalis toward CHX and BAC, and in S. aureus toward CPC. Adapted E. coli strains showed different protein expression as compared with the wildtype strain. Conclusion Antiseptics showed limited antimicrobial efficacy toward mature biofilms when applied for clinically relevant treatment periods. Bacteria showed phenotypic adaptation upon repeated sub-inhibitory exposure. Clinical relevance Clinicians should be aware that wide-spread use of antiseptics may pose the risk of inducing resistances in oral bacteria.

During orthodontic tooth movement (OTM) mechanical forces trigger pseudo-inflammatory, osteoclastogenic and remodelling processes in the periodontal ligament (PDL) that are mediated by PDL fibroblasts via the expression of various signalling molecules. Thus far, it is unknown whether these processes are mainly induced by mechanical cellular deformation (mechanotransduction) or by concomitant hypoxic conditions via the compression of periodontal blood vessels. Human primary PDL fibroblasts were randomly seeded in conventional six-well cell culture plates with O2-impermeable polystyrene membranes and in special plates with gas-permeable membranes (Lumox®, Sarstedt), enabling the experimental separation of mechanotransducive and hypoxic effects that occur concomitantly during OTM. To simulate physiological orthodontic compressive forces, PDL fibroblasts were stimulated mechanically at 2 g·cm−2 for 48 h after 24 h of pre-incubation. We quantified the cell viability by MTT assay, gene expression by quantitative real-time polymerase chain reaction (RT-qPCR) and protein expression by western blot/enzyme-linked immunosorbent assays (ELISA). In addition, PDL-fibroblast-mediated osteoclastogenesis (TRAP+ cells) was measured in a 72-h coculture with RAW264.7 cells. The expression of HIF-1α, COX-2, PGE2, VEGF, COL1A2, collagen and ALPL, and the RANKL/OPG ratios at the mRNA/protein levels during PDL-fibroblast-mediated osteoclastogenesis were significantly elevated by mechanical loading irrespective of the oxygen supply, whereas hypoxic conditions had no significant additional effects. The cellular–molecular mediation of OTM by PDL fibroblasts via the expression of various signalling molecules is expected to be predominantly controlled by the application of force (mechanotransduction), whereas hypoxic effects seem to play only a minor role. In the context of OTM, the hypoxic marker HIF-1α does not appear to be primarily stabilized by a reduced O2 supply but is rather stabilised mechanically.

Autophagy (cellular self-consumption) is a crucial adaptation mechanism during cellular stress conditions. This study aimed to examine how this important process is regulated in human periodontal ligament (PDL) fibroblasts by mechanical and inflammatory stress conditions and whether the mammalian target of rapamycin (mTOR) signaling pathway is involved. Autophagy was quantified by flow cytometry. Qualitative protein phosphorylation profiling of the mTOR pathway was carried out. Effects of mTOR regulation were assessed by quantification of important synthesis product collagen 1, cell proliferation and cell death with real-time PCR and flow cytometry. Autophagy as a response to mechanical or inflammatory treatment in PDL fibroblasts was dose and time dependent. In general, autophagy was induced by stress stimulation. Phosphorylation analysis of mTOR showed regulatory influences of mechanical and inflammatory stimulation on crucial target proteins. Regulation of mTOR was also detectable via changes in protein synthesis and cell proliferation. Physiological pressure had cell-protective effects (p = 0.025), whereas overload increased cell death (p = 0.003), which was also promoted in long-term inflammatory treatment (p < 0.001). Our data provide novel insights about autophagy regulation by mechanical and inflammatory stress conditions in human PDL fibroblasts. Our results suggest some involvement of the mTOR pathway in autophagy and cell fate regulation under the named conditions.

The present study tested the combination of mandibular and dental dimensions for sex determination using machine learning. Lateral cephalograms and dental casts were used to obtain mandibular and mesio-distal permanent teeth dimensions, respectively. Univariate statistics was used for variables selection for the supervised machine learning model (alpha = 0.05). The following algorithms were trained: logistic regression, gradient boosting classifier, k-nearest neighbors, support vector machine, multilayer perceptron classifier, decision tree, and random forest classifier. A threefold cross-validation approach was adopted to validate each model. The areas under the curve (AUC) were computed, and ROC curves were constructed. Three mandibular-related measurements and eight dental size-related dimensions were used to train the machine learning models using data from 108 individuals. The mandibular ramus height and the lower first molar mesio-distal size exhibited the greatest predictive capability in most of the evaluated models. The accuracy of the models varied from 0.64 to 0.74 in the cross-validation stage, and from 0.58 to 0.79 when testing the data. The logistic regression model exhibited the highest performance (AUC = 0.84). Despite the limitations of this study, the results seem to show that the integration of mandibular and dental dimensions for sex prediction would be a promising approach, emphasizing the potential of machine learning techniques as valuable tools for this purpose.

Non-steroidal anti-inflammatory drugs (NSAID) are used to alleviate pain sensations during orthodontic therapy but are also assumed to interfere with associated pseudo-inflammatory reactions. In particular, the effects of partially selective COX-2 inhibition over the constitutively expressed COX-1 (11:1) on periodontal cells and tissue, as induced by the NSAID meloxicam, remain unclear. We investigate possible adverse side-effects and potentially useful beneficial effects during orthodontic therapy and examine underlying cellular and tissue reactions. We randomly assigned 63 male Fischer344 rats to three consecutive experiments of 21 animals each (cone-beam computed tomography; histology/serology; reverse-transcription quantitative real-time polymerase chain reaction) in three experimental groups ( n  = 7; control; orthodontic tooth movement [OTM] of the first/second upper left molars [NiTi coil spring, 0.25 N]; OTM with a daily oral meloxicam dose of 3 mg/kg). In vitro, we stimulated human periodontal ligament fibroblasts (hPDL) with orthodontic pressure (2 g/cm 2 ) with/without meloxicam (10 μM). In vivo, meloxicam significantly reduced serum C-reactive protein concentration, tooth movement velocity, orthodontically induced dentine root resorption (OIRR), osteoclast activity and the relative expression of inflammatory/osteoclast marker genes within the dental-periodontal tissue, while presenting good gastric tolerance. In vitro, we observed a corresponding significant decrease of prostaglandin E 2 /interleukin-6/RANKL(−OPG) expression and of hPDL-mediated osteoclastogenesis. By inhibiting prostaglandin synthesis, meloxicam seems to downregulate hPDL-mediated inflammation, RANKL-induced osteoclastogenesis and, consequently, tooth movement velocity by about 50%, thus limiting its suitability for analgesia during orthodontic therapy. However, its protective effects regarding OIRR and good tolerance profile suggest future prophylactic application, which merits its further investigation.

Objective To perform a systematic review/meta-analysis to elucidate the scientific basis for the association between genetic variations and risk of external apical root resorption (EARR) in orthodontic patients. Materials and methods Four databases (PubMed, Web of Science, Scopus, LILACS) were electronically searched until November 22, 2020, followed by manual and gray literature search. Case-control or cross-sectional studies that evaluated genes involved in the susceptibility of orthodontic patients to EARR were eligible. Two reviewers applied the inclusion and exclusion criteria, extracted qualitative data, as well as assessed methodological quality using instrument proposed for genetic studies. For synthesis results, narrative and quantitative data (meta-analysis) were performed. The certainty of the evidence was tested using the GRADE Working Group approach. Results Of 201 articles in total, 16 studies were included in the review. Of these, 11 presented moderate and 5 of high methodological quality. In the narrative analysis, from 16 studies, 15 studies (10 genes) showed a significant association with EARR and 9 studies were included in the meta-analysis. Only the polymorphism rs208294 in P2RX7 (dominant model) was associated with EARR (OR = 0.52, 95%CI = 0.29–0.95, p  = 0.03) and presented a very low certainty of the evidence. Conclusion Narrative analyses of individual studies demonstrated an association of many genes. The number of studies for each genetic variation was very low, and methodological heterogeneity between the studies was observed. Quantitative analyses (meta-analysis) could only show an involvement for P2RX7 (rs208294) in the risk of orthodontic patients to EARR at a very low certainty of evidence. (CRD42018085411). Clinical relevance The knowledge regarding the molecular aspects involved in the etiology of EARR will allow orthodontists to use a personalized treatment and early diagnosis of risk patients. This systematic review demonstrates that more studies are necessary to unravel the role of genetic variation for patients’ risk to EARR during orthodontic tooth movement.