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Purpose It is thought that orthodontic forces initially reduce periodontal blood flow during orthodontic tooth movement (OTM) via tissue compression with cells responding to concomitant oxygen deprivation with expression of vascular endothelial growth factor (VEGF) triggering angiogenesis via binding to its receptor VEGFR‑2. To test this hypothesis, we performed a pilot study to establish a protocol for molecular magnetic resonance imaging (MRI) of rat jaws administering a VEGFR-2-specific contrast agent. Methods Mesial OTM of a first upper left rat molar was initiated in one male Fischer 344 rat 4 days prior to MRI by insertion of an elastic band between the first and second upper molars with the contralateral side left untreated (internal control). T1-weighted MRI sequences including dynamic contrast-enhanced MRI (DCE-MRI) were recorded before and after administration of a molecular VEGFR‑2 MRI marker with a 7 T MRI dedicated for small animal use. Results After injection of anti-VEGFR2-albumin-gadolinium-DTPA, volume enhancement on T1-weighted images was increased at the OTM side distally of the moved first upper molar (M1) compared to the control side, whereas the T1 relaxation time was reduced on the OTM side. DCE-MRI resulted in an increased area under the curve (AUC), whereas time-to-peak (TTP) and washout rate were reduced during OTM distally of the moved M1 compared to the contralateral side. Conclusions OTM resulted in uptake of the VEGFR-2-specific MRI contrast agent in tension areas of the periodontal ligament. The imaging protocol presented here is useful for the assessment of VEGFR‑2 expression in tension areas of the periodontal ligament in vivo. Zielsetzung Es wird angenommen, dass kieferorthopädische Kräfte initial den parodontalen Blutfluss während der kieferorthopädischen Zahnbewegung (OTM) durch Gewebekompression reduzieren, wobei die beteiligten Zellen auf einen begleitenden Sauerstoffmangel mit einer Expression des vaskulären endothelialen Wachstumsfaktors (VEGF) reagieren, der über die Bindung an seinen Rezeptor VEGFR‑2 die Angiogenese induziert. Um diese Hypothese zu untersuchen, führten wir eine Pilotstudie durch, um ein Protokoll für die molekulare Magnetresonanztomographie (MRT) von Rattenkiefern nach Verabreichung eines VEGFR-2-spezifischen Kontrastmittels zu etablieren. Material und Methoden Bei einer männlichen Fischer-344-Ratte wurde der erste obere Molar (M1) auf der linken Kieferseite 4 Tage vor der MRT durch Einbringen eines elastischen Bandes zwischen dem ersten und zweiten oberen Molaren mesialisiert, wobei die kontralaterale Seite unbehandelt blieb (interne Kontrolle). T1-gewichtete MRT-Sequenzen einschließlich dynamischer kontrastmittelunterstützter MRT (DCE-MRT) wurden vor und nach der Verabreichung eines molekularen VEGFR-2-MRT-Markers mit einem 7‑Tesla-MRT für Kleintiere aufgezeichnet. Ergebnisse Nach Injektion von Anti-VEGFR2-Albumin-Gadolinium-DTPA war die Volumenanhebung auf T1-gewichteten Bildern auf der OTM-Seite distal des bewegten ersten oberen Molaren (M1) im Vergleich zur Kontrollseite erhöht, während die T1-Relaxationszeit auf der OTM-Seite verkürzt war. Die DCE-MRT führte zu einer erhöhten Fläche unter der Kurve (AUC), während die TTP-Zeit bis zum Spitzenwert und die Auswaschungsrate während der OTM distal des bewegten M1 im Vergleich zur kontralateralen Seite reduziert waren. Schlussfolgerungen Die kieferorthopädische Zahnbewegung führte zur Aufnahme des VEGFR-2-spezifischen MRT-Kontrastmittels in Zugzonen des Parodontalligaments. Das hier vorgestellte Bildgebungsprotokoll hat sich für die In-vivo-Beurteilung der VEGFR-2-Expression in Zugzonen des Parodonts als nützlich erwiesen.

Purpose It is thought that orthodontic forces initially reduce periodontal blood flow during orthodontic tooth movement (OTM) via tissue compression with cells responding to concomitant oxygen deprivation with expression of vascular endothelial growth factor (VEGF) triggering angiogenesis via binding to its receptor VEGFR‑2. To test this hypothesis, we performed a pilot study to establish a protocol for molecular magnetic resonance imaging (MRI) of rat jaws administering a VEGFR-2-specific contrast agent. Methods Mesial OTM of a first upper left rat molar was initiated in one male Fischer 344 rat 4 days prior to MRI by insertion of an elastic band between the first and second upper molars with the contralateral side left untreated (internal control). T1-weighted MRI sequences including dynamic contrast-enhanced MRI (DCE-MRI) were recorded before and after administration of a molecular VEGFR‑2 MRI marker with a 7 T MRI dedicated for small animal use. Results After injection of anti-VEGFR2-albumin-gadolinium-DTPA, volume enhancement on T1-weighted images was increased at the OTM side distally of the moved first upper molar (M1) compared to the control side, whereas the T1 relaxation time was reduced on the OTM side. DCE-MRI resulted in an increased area under the curve (AUC), whereas time-to-peak (TTP) and washout rate were reduced during OTM distally of the moved M1 compared to the contralateral side. Conclusions OTM resulted in uptake of the VEGFR-2-specific MRI contrast agent in tension areas of the periodontal ligament. The imaging protocol presented here is useful for the assessment of VEGFR‑2 expression in tension areas of the periodontal ligament in vivo.

Orthodontic tooth movement to therapeutically align malpositioned teeth is supposed to impact blood flow in the surrounding tissues. Here, we evaluated actual vascularization in the tension area of the periodontal ligament during experimental tooth movement in rats (N = 8) with magnetic resonance imaging (MRI). We inserted an elastic band between the left upper first and the second rat molar, the right side was not treated and served as control. After four days of tooth movement, we recorded T1-weighted morphologic and dynamic-contrast-enhanced MRI sequences with an animal-specific 7 Tesla MRI to assess of local vascularization. Furthermore, we quantified osteoclasts and monocytes in the periodontal ligament, which are crucial for orthodontic tooth movement, root resorptions as undesirable side effects, as well as the extent of tooth movement using paraffine histology and micro-CT analysis. Data were tested for normal distribution with Shapiro&ndash, Wilk tests followed by either a two-tailed paired t-test or a Wilcoxon matched-pairs signed rank test. Significant orthodontic tooth movement was induced within the four days of treatment, as evidenced by increased osteoclast and monocyte activity in the periodontal ligament as well as by &micro, CT analysis. Contrast enhancement was increased at the orthodontically-treated side distally of the moved upper first left molar, indicating increased vascularization at the tension side of the periodontal ligament. Accordingly, we detected reduced time-to-peak and washout rates. Our study using MRI to directly assess local vascularization thus seems to confirm the hypothesis that perfusion is enhanced in tension zones of the periodontal ligament during orthodontic tooth movement.

The human oral microbiota consists of over 700 widespread taxa colonizing the oral cavity in several anatomically diverse oral niches. Lately, sequencing of the 16S rRNA genes has become an acknowledged, culture-independent method to characterize the oral microbiota. However, only a small amount of data are available concerning microbial differences between oral niches in periodontal health and disease. In the context of periodontitis, the cytokine expression in the gingival crevicular fluid has been studied in detail, whereas little is known about the cytokine profile in hard and soft tissue biofilms. In order to characterize oral niches in periodontal health, the oral microbiota and cytokine pattern were analyzed at seven different sites (plaque (P), gingival crevicular fluid (GCF), saliva (S), tongue (T), hard palate (HP), cheek (C) and sublingual area (U)) of 20 young adults using next-generation sequencing and multiplex immunoassays. Site-specific microbial compositions were detected, which clustered into three distinct metaniches (&ldquo, P-GCF&rdquo, &ldquo, S-T-HP&rdquo, and &ldquo, C-U&rdquo, ) and were associated with niche-/metaniche-specific cytokine profiles. Our findings allow the definition of distinct metaniches according to their microbial composition, partly reflected by their cytokine profile, and provide new insights into microenvironmental similarities between anatomical diverse oral niches.

Apart from periodontal ligament fibroblasts, immune cells like macrophages also play an important mediating role in orthodontic tooth movement (OTM). Upon orthodontic force application to malpositioned teeth, macrophages in the periodontal ligament get exposed to both mechanical strain and hypoxic conditions (via a compression of blood vessels). In this study, we assessed the relative impact of orthodontically induced mechanical strain and hypoxic conditions on macrophages for the mediation and regulation of OTM. Macrophages were stimulated with physiological orthodontic compressive forces of 2 g/cm(2) for 4 h and 24 h on gas-impermeable or gas-permeable cell culture plates under normoxic or hypoxic cell culture conditions. We quantified expression of genes involved in inflammation (Tnf,Il-6, andCox-2), extracellular remodelling (Mmp-9), and angiogenesis (Vegf) by RT-qPCR. Furthermore, we analysed HIF-1 alpha, prostaglandin-E2, and VEGF protein expression via immunoblotting or ELISA. Mechanical strain and oxygen supply both differentially affected expression of genes and proteins involved in inflammation and angiogenesis. In this context, we found that HIF-1 alpha protein levels were elevated by combined mechanical strain and hypoxic conditions, whereas gas-permeable plates providing sufficient oxygen supply prevented HIF-1 alpha stabilization at the protein level after pressure application on macrophages. Our results thus indicate that macrophages involved in the mediation of OTM are affected by and respond differently to hypoxic conditions and mechanical compressive strain, which occur concomitantly during OTM, than periodontal ligament fibroblasts (PDLF), thus indicating different roles of these cells in the regulation of OTM at the cellular-molecular level. We further observed that contrary to PDLF HIF-1 alpha stabilization in macrophages is rather induced via the decreased oxygen supply associated with OTM than via mechanotransduction by mechanical strain.