Effect of micro-osteoperforations on the gene expression profile of the periodontal ligament of orthodontically moved human teeth.

OBJECTIVES: This study aimed to evaluate the effect of micro-osteoperforations (MOPs) on the gene expression profile of the periodontal ligament (PDL) of orthodontically moved teeth. MATERIALS AND METHODS: Fifteen participants were randomly assigned into two groups: tooth movement only (Tr1, n = 7) and tooth movement supplemented with MOPs (Tr2, n = 8). In each subject, orthodontic tooth movement (OTM) was performed on premolar in one side, while no force was applied on contralateral premolar (Unt, n = 15). Seven days after loading, premolars were extracted for orthodontic reasons. RNA extraction from PDL and subsequent RNA-sequencing were performed. False discovery rates (Padj < 0.05) and log2 fold change (+ / - 1.5) thresholds were used to identify sets of differentially expressed genes (DEGs) among the groups. DEGs were analyzed with gene ontology enrichment, KEGG, and network analysis. RESULTS: Three hundred thirty-one DEGs were found between Tr1 and Unt, and 356 between Tr2 and Unt. Although, there were no significantly DEGs between Tr2 and Tr1, DEGs identified exclusively in Tr1 vs. Unt were different from those identified exclusively in Tr2 vs. Unt. In Tr1, genes were related to bone metabolism processes, such as osteoclast and osteoblast differentiation. In Tr2, genes were associated to inflammation processes, like inflammatory and immune responses, and cellular response to tumor necrosis factor. CONCLUSIONS: MOPs do not significantly alter the PDL gene expression profile of orthodontically moved human teeth. This study provides for the first time evidence on the whole PDL gene expression profiles associated to OTM in humans. Novel biomarkers for OTM are suggested for additional research. Clinical relevance The identified biomarkers provide new insights into the molecular mechanisms that would occur when OTM is supplemented with MOPs. These markers are expected to be useful in the near future for the application of personalized strategies related to the OTM.

Influence of orthodontic loading on biomarkers levels around miniscrews.

OBJECTIVE: The aim of this study was to evaluate the levels of Interleukin-1α (IL-1α), Interleukin-1ß (IL-1ß), Interleukin-1 receptor antagonist (IL-1Ra), Interleukin-10 (IL-10), Interleukin-13 (IL-13), Vascular endothelial growth factor (VEGF), Granulocyte-colony stimulating factor (G-CSF), and Growth related oncogene (GRO) in the peri-miniscrew implant crevicular fluid (MICF) under orthodontic loading. DESIGN: The study sample comprised 14 miniscrews immediately loaded and 17 unloaded ones. A load of 200gF was immediately applied to the miniscrews in the loaded group after the placement surgery. Peri-miniscrew implant crevicular fluid was collected at baseline, at day 7, and at day 21. The levels of the biomarkers were measured using a multiplexed bead immunoassay. Intergroup comparisons were made using Mann-Whitney test. Friedman and Dunn's multiple comparison tests were used to evaluate intragroup differences over time. RESULTS: Although no statistical differences were observed between the groups at any time point for any of the 8 biomarkers evaluated, there was a statistically significant increase (p < 0.02) in the levels of all the biomarkers over time on both groups. CONCLUSIONS: An immediate loading of 200gF does not alter the balance in the inflammatory response in peri-miniscrew tissues.

Global gene expression profile of periodontal ligament cells submitted to mechanical loading: A systematic review.

OBJECTIVE: To evaluate the evidence reporting gene expression array data of human in vitro cultured periodontal ligament cells (PDLCs) submitted to static mechanical loading compared to a control group. DESIGN: Systematic searches were performed in MEDLINE/PubMed, Scopus, Web of Science, Virtual Health Library, The Cochrane Library and the System for Information on Grey Literature in Europe up to June 2019. A narrative synthesis was performed to summarize differentially expressed genes (DEGs). These were grouped according to the culture method (2D or 3D), force type (compression or tension) and observation time. Additionally, gene ontology (GO) analysis was performed using the Database for Annotation Visualization and Integrated Discovery. The risk of bias (RoB) and certainty of evidence (CoE) were assessed using a modified CONSORT checklist and the GRADE tool, respectively. RESULTS: Of eight studies included (all rated as having moderate RoB), only two provided the complete list of DEGs and four studies performed GO, gene network or pathways analysis. "Cell proliferation", "cell-cell signaling", "response to hypoxia and to mechanical stimulus" were among the significantly enriched biological processes in 3D-cultured compressed PDLCs (moderate CoE); while "collagen catabolic process", "extracellular matrix organization" and "cell proliferation" were associated with DEGs of 3D-cultured PDLCs submitted to tension (very low CoE). Biological processes significantly enriched in 2D-cultured PDLCs under compression were "extracellular matrix organization", "canonical glycolysis" and "glycolytic process" (very low CoE). CONCLUSION: Genes such as NR4A2, NR4A3, NAMPT, PGK1, and REDD1 are suggested as novel biomarkers for orthodontic tooth movement. Limited amount of evidence on the complete gene expression profile and the high heterogeneity in methodologies make it impossible to obtain definite conclusions. New studies following standardized and well-designed in vitro model and reporting complete gene expression datasets are needed.

Reproducibility of digital indirect bonding technique using three-dimensional (3D) models and 3D-printed transfer trays.

OBJECTIVE: To evaluate the reproducibility of digital tray transfer fit on digital indirect bonding by analyzing the differences in bracket positions. MATERIALS AND METHODS: Digital indirect bonding was performed by positioning brackets on digital models superimposed by tomography using Ortho Analyzer (3Shape) software. Thirty-three orthodontists performed indirect bonding on prototyped models of the same malocclusion using prototyped transfer trays for two types of brackets (MiniSprint Roth and BioQuick self-ligating). The models with brackets were scanned using an intraoral scanner (Trios, 3Shape). Superimpositions were made between the digital models obtained after indirect bonding and those from the original virtual setup. To analyze the differences in bracket positions, three planes were examined for each bracket: vertical, horizontal, and angulation. Three orthodontists repeated indirect bonding after 15 days, and Bland-Altman plots and intraclass correlation coefficients were used to evaluate inter- and intraevaluator reproducibility and reliability, respectively. Repeated-measures analysis of variance (ANOVA) was used to analyze the differences between bracket positions, and multivariate ANOVA was used to evaluate the influence of orthodontists' experience on the results. RESULTS: Differences between bracket positions were not statistically significant, except mesial-distal discrepancies in the BioQuick group (P = .016). However, differences were not clinically significant (horizontal varied from 0.04 to 0.13 mm; angulation, 0.45° to 2.03°). There was no significant influence of orthodontist experience and years of clinical practice on bracket positions (P = .314 and P = .158). The reproducibility among orthodontists was confirmed. CONCLUSIONS: The reproducibility of digital indirect bonding was confirmed in terms of bracket positions using three-dimensional printed transfer trays.