Experimental Tooth Movement Research Articles

Effect of Caffeic Acid Phenethyl Ester Provision on Fibroblast Growth Factor-2, Matrix Metalloproteinase-9 Expression, Osteoclast and Osteoblast Numbers during Experimental Tooth Movement in Wistar Rats (Rattus norvegicus).

Objectives To investigate the effect of caffeic acid phenethyl ester (CAPE) provision on matrix metalloproteinase-9 (MMP-9), fibroblast growth factor-2 (FGF-2) expression, osteoclast and osteoblast numbers during experimental orthodontic tooth movement (OTM) in male Wistar rats ( Rattus norvegicus ). Materials and Methods Forty-eight healthy male Wistar rats ( R. norvegicus ), 16 to 20 weeks old with 200 to 250 g body weight (bw) were divided into several groups as follows: K1: OTM for 3 days; K2: OTM for 7 days; K3: OTM for 14 days; KP1: OTM and CAPE for 3 days; KP2: OTM and CAPE for 7 days; and KP3: OTM and CAPE for 14 days. A nickel titanium closed coil spring 8.0 mm long with 10 g/mm 2 was installed between the upper left first molar and upper central incisor to move molar mesially. CAPE provision with a dose of 20 mg/kg bw of animal studies was done per orally. Immunohistochemistry was done to examine MMP-9 expression and osteoclast number in compression side as well as FGF-2 expression and osteoblast number in tensile side of the OTM. Statistical Analysis One-way analysis of variance test and Tukey’s honest significant difference test were performed to determine the difference between the groups ( p < 0.05). Results MMP-9 expression and osteoclast numbers in the compression side were significantly different between the groups. Similarly, FGF-2 expression and osteoclast numbers in the tensile side were significantly different between the groups. Conclusions CAPE provision during OTM increases the number of osteoblasts and the FGF-2 expression significantly in the tensile side. Osteoclast numbers and MMP-9 expression significantly decrease in the compression side.

Local Vascularization during Orthodontic Tooth Movement in a Split Mouth Rat Model-A MRI Study.

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–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 µCT 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.

CXCL5, CXCL8, and CXCL10 regulation by bacteria and mechanical forces in periodontium

ObjectiveThe aim of the present study was to evaluate the expressions of CXCL5, CXCL8, and CXCL10 in periodontal cells and tissues in response to microbial signals and/or biomechanical forces. MethodsHuman gingival biopsies from inflamed and healthy sites were used to examine the chemokine expressions and protein levels by real-time PCR and immunohistochemistry. The chemokines were also investigated in gingival biopsies from rats submitted to experimental periodontitis and/or tooth movement. Furthermore, chemokine levels were determined in human periodontal fibroblasts stimulated by the periodontopathogen Fusobacterium nucleatum and/or constant tensile forces (CTS) by real-time PCR and ELISA. Additionally, gene expressions were evaluated in periodontal fibroblasts exposed to F. nucleatum and/or CTS in the presence and absence of a MAPK inhibitor by real-time PCR. ResultsIncreased CXCL5, CXCL8, and CXCL10 levels were observed in human and rat gingiva from sites of inflammation as compared with periodontal health. The rat experimental periodontitis caused a significant (p<0.05) increase in alveolar bone resorption, which was further enhanced when combined with tooth movement. In vitro, F. nucleatum caused a significant upregulation of CXCL5, CXCL8, and CXCL10 at 1 day. Once the cells were exposed simultaneously to F. nucleatum and CTS, the chemokines regulation was significantly enhanced. The transcriptional findings were also observed at protein level. Pre-incubation with the MEK1/2 inhibitor significantly (p<0.05) inhibited the stimulatory actions of F. nucleatum either alone or in combination with CTS on the expression levels of CXCL5, CXCL8, and CXCL10 at 1d. ConclusionsOur data provide original evidence that biomechanical strain further increases the stimulatory actions of periodontal bacteria on the expressions of these chemokines. Therefore, biomechanical loading in combination with periodontal infection may lead to stronger recruitment of immunoinflammatory cells to the periodontium, which might result in an aggravation of periodontal inflammation and destruction.

Daidzein induces bone morphogenetic protein-2 and runt-related transcription 2 on periodontal ligament cells after experimental tooth movement

ABSTRACT Purpose To analysis, daidzein increases the expression of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor 2 (Runx2) after experimental tooth movement (EXTM). Materials and Methods 36 Wistar rats were randomly divided into the EXTM group and EXTM with daidzein group (EXTM+DZ group). After EXTM, the rats in the EXTM+DZ group were treated with daidzein (10 mg/kg/day). Micro-computed tomography (CT) analysis revealed the bone mineral density (BMD), ratio of bone volume to tissue volume (BV/TV), and ratio of relapse. Histopathological changes were examined by immunohistochemical staining for BMP-2 and Runx2. Human PDLCs were subjected to tension force and treated with 10 μg/mL daidzein. The expression of BMP-2 and Runx2 by daidzein was confirmed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results The EXTM+DZ group showed a significantly decreased ratio of relapse and increased BMD and BV/TV as compared to the EXTM group. The ratio of BMP-2 – and Runx-2 –positive cells in the EXTM+DZ group was higher than that in the EXTM group. Moreover, daidzein upregulated the mRNA expression and protein levels of BMP-2 and Runx2 in a time-dependent manner. Conclusion These results suggested that daidzein decreased the ratio of relapse through BMP-2 and Runx2 expression.

In Vivo Ca2+ Imaging of the Insular Cortex during Experimental Tooth Movement

Pain and discomfort are common problems for patients undergoing orthodontic treatment. We have demonstrated that cortical excitation propagation in the somatosensory and insular cortices (IC) induced by electrical stimulation of the periodontal ligament (PDL) is facilitated 1 d after experimental tooth movement (ETM). However, it is necessary to examine ETM-induced changes in neural responses at a single-cell level to understand the mechanisms of cortical plastic changes, in which excitatory glutamatergic and inhibitory GABAergic neurons are intermingled to form cortical local circuits. We performed in vivo 2-photon Ca2+ imaging by loading the Ca2+ indicator Oregon Green BAPTA with the astrocyte marker sulforhodamine. We focused on the IC region that exhibited the largest neural response to maxillary PDL (mxPDL) stimulation using a VGAT-Venus transgenic rat that expresses venus fluorescent protein in GABAergic neurons and discerned changes in the neural activities of each cortical neuronal subtype before and during ETM treatment of the maxillary incisor and first molar. Notably, 1 d after ETM treatment (1d-ETM), the number of neurons responding to mxPDL stimulation increased from 47.6% to 64.2% in excitatory neurons and from 44.5% to 66.2% in inhibitory neurons. On the other hand, only 3% to 4% of excitatory and inhibitory neurons responded to mandibular molar PDL (mbPDL) stimulation in control rats, and the 1d-ETM group showed significant increases in excitatory (14.0%) and inhibitory neurons (22.5%) responding to mbPDL stimulation. Interestingly, most mbPDL-responding neurons also responded to mxPDL stimulation. The population of excitatory and inhibitory neurons that responded only to mxPDL stimulation was comparable between the control and 1d-ETM groups. The facilitative responses in the 1d-ETM group had almost recovered 7 d after ETM treatment. These results suggest that ETM induces parallel increases in PDL-responding neurons and changes some insensitive neurons to respond to both mxPDL and mbPDL stimulation.

Involvement of astrocytes activation in orofacial hyperalgesia induced by experimental tooth movement.

The study aimed to investigate the involvement of astrocytes in the medullary dorsal horn (MDH) in the orofacial hyperalgesia induced by experimental tooth movement (ETM) and related mechanism. Experimental tooth movement was produced with nickel-titanium alloy closed-coil spring fixed between the left maxillary first molar and the left upper incisor. Fluorocitrate was administrated through medullary subarachnoid at 3days after ETM. Pressure pain threshold (PPT) in masseter cutaneous area was measured. The expression of glial fibrillary acidic protein (GFAP) and c-Fos in MDH was measured using immunofluoroscence staining. The expression of interleukin-1β (IL-1β) and phosphorylated N-methyl-D-aspartic acid (NMDA) receptor subunit NR1 (p-NR1) was measured with Western blotting. Experimental tooth movement-induced orofacial hyperalgesia from 1 to 9days as the PPT was significantly reduced (P<.05). Immunofluoroscence staining showed that the expression of c-Fos in MDH was dramatically upregulated at 1day and 3days after ETM, while GFAP expression with both immunofluoroscence staining and Western blotting was significantly enhanced at 3days and 7days after ETM. Western blotting analysis indicated that the expression of IL-1β and p-NR1 in MDH was significantly enhanced at 3days after ETM. Furthermore, we found that fluorocitrate administration at 3days after ETM could markedly suppress the expression of c-Fos, GFAP, IL-1β and p-NR1 and attenuate the reduction of PPT induced by ETM. Astrocyte activation in MDH is involved in the mechanical hyperalgesia, and the subsequent upregulated IL-1β and overexpression of p-NR1 may participate in this process.

Effect of resveratrol on the hyperexcitability of nociceptive neurons associated with ectopic hyperalgesia induced by experimental tooth movement.

The present study investigated whether, under in vivo conditions, systemic administration of resveratrol attenuates the experimental tooth movement-induced ectopic hyperalgesia associated with hyperexcitability of nociceptive trigeminal spinal nucleus caudalis (SpVc) neurons. The threshold of escape from mechanical stimulation applied to the ipsilateral whisker pad in rats exposed to experimental tooth movement was significantly lower than seen in control rats from day 1 to 3 following movement of the right maxillary first molar tooth. The lowered mechanical threshold in the rats exposed to experimental tooth movement had almost returned to the level of sham-treated naïve rats at day 3 following administration of resveratrol. The mean mechanical threshold of nociceptive SpVc neurons was significantly lower after experimental tooth movement but the lower threshold could be reversed by administration of resveratrol. The higher discharge frequency of nociceptive SpVc neurons for noxious mechanical stimuli observed in rats exposed to experimental tooth movement was statistically significantly lower following resveratrol administration. These results suggest that resveratrol attenuates experimental tooth movement-induced mechanical ectopic hyperalgesia via suppression of peripheral and/or central sensitization. These findings support the idea that resveratrol, a complementary alternative medicine, is a potential therapeutic agent for the prevention of experimental tooth movement-induced ectopic hyperalgesia.

Comparative assessment of mouse models for experimental orthodontic tooth movement

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.

Involvement of interleukins-17 and -34 in exacerbated orthodontic root resorption by jiggling force during rat experimental tooth movement

BackgroundOrthodontically induced root resorption (OIRR) is considered as an undesirable and unpredictable sequel of orthodontic treatment. Recent reports demonstrated that interleukin (IL)-17/IL-34, and T cells secrete inflammatory/osteoclastogenic cytokines, which might stimulate osteoclastogenesis/bone resorption. However, little is known about the role played by IL-17/IL-34 in OIRR. The present study was aimed at investigating the odontoclastic expression pattern of IL-17 and IL-34 in resorbed cementum during different experimental tooth movements in vivo. MethodsTwenty-four 8-week-old male Wistar rats were divided into four groups: control group, optimal force group (10 g), heavy force group (50 g), and jiggling force group (compression and tension, repetition; 10 g). After 7, 14, and 21 days, the expression levels of IL-17 and IL-34 protein in the resorbed cementum were analyzed using immunohistochemical methods. ResultsOn day 21, the immunoreactivity for IL-17 and IL-34 in resorbed roots in the jiggling force group was stronger than that in the heavy force and optimal force groups. Moreover, the number of IL-17-positive and IL-34–positive odontoclasts was significantly increased in the jiggling force group compared with those in the other groups on day 21. ConclusionsThese results suggest that jiggling forces might exacerbate OIRR compared with heavy forces, as evidenced by the increased expression of IL-17 and IL-34 in odontoclasts obtained from resorbed roots.

Delayed tooth movement in Runx2+/− mice associated with mTORC2 in stretch-induced bone formation

Runt-related transcription factor 2 (Runx2) is an essential transcription factor for osteoblast differentiation, and is activated by mechanical stress to promote osteoblast function. Cleidocranial dysplasia (CCD) is caused by mutations of RUNX2, and CCD patients exhibit malocclusion and often need orthodontic treatment. However, treatment is difficult because of impaired tooth movement, the reason of which has not been clarified. We examined the amount of experimental tooth movement in Runx2+/− mice, the animal model of CCD, and investigated bone formation on the tension side of experimental tooth movement in vivo. Continuous stretch was conducted to bone marrow stromal cells (BMSCs) as an in vitro model of the tension side of tooth movement. Compared to wild-type littermates the Runx2+/− mice exhibited delayed experimental tooth movement, and osteoid formation and osteocalcin (OSC) mRNA expression were impaired in osteoblasts on the tension side of tooth movement. Runx2 heterozygous deficiency delayed stretch-induced increase of DNA content in BMSCs, and also delayed and reduced stretch-induced alkaline phosphatase (ALP) activity, OSC mRNA expression, and calcium content of BMSCs in osteogenic medium. Furthermore Runx2+/− mice exhibited delayed and suppressed expression of mammalian target of rapamycin (mTOR) and rapamycin-insensitive companion of mTOR (Rictor), essential factors of mTORC2, which is regulated by Runx2 to phosphorylate Akt to regulate cell proliferation and differentiation, in osteoblasts on the tension side of tooth movement in vivo and in vitro. Loss of half Runx2 gene dosage inhibited stretch-induced PI3K dependent mTORC2/Akt activity to promote BMSCs proliferation. Furthermore, Runx2+/− BMSCs in osteogenic medium exhibited delayed and suppressed stretch-induced expression of mTOR and Rictor. mTORC2 regulated stretch-elevated Runx2 and ALP mRNA expression in BMSCs in osteogenic medium. We conclude that Runx2+/− mice present a useful model of CCD patients for elucidation of the molecular mechanisms in bone remodeling during tooth movement, and that Runx2 plays a role in stretch-induced proliferation and osteogenesis in BMSCs via mTORC2 activation.

Baicalin inhibits root resorption during tooth movement in a rodent model

ObjectiveBaicalin mediates bone metabolism and has shown protective activity against periodontal tissue damage in a rat model of periodontitis. Therefore, we hypothesized that baicalin may inhibit the root resorption that occurs during orthodontic tooth movement and examined its effect on the histological changes in periodontal tissue that occur during tooth movement. MethodsFirst molars of rats were subjected to traction using excessive orthodontic force to produce a root resorption model. Rats in the baicalin group received baicalin for 3 weeks during tooth movement, and the amount of first molar movement on day 21 after the initiation of traction was measured by three-dimensional micro-computed tomography analysis. After tooth movement, tissue samples from the mesial and tension sides were collected, and successive horizontal sections were prepared and examined using hematoxylin–eosin and tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical staining for the receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG). The severity of root resorption was also determined by histological analysis. ResultsThere was no significant intergroup difference in tooth movement during the experimental exaggerated tooth movement. In comparison with the control group, the baicalin-treated group showed increased OPG expression, suppressed RANKL expression, and significantly fewer TRAP-positive cells in the first molars. The root resorption area was significantly smaller in the baicalin group. ConclusionsTreatment with baicalin prevented root resorption without preventing tooth movement. Baicalin may be useful for the management of root resorption during orthodontic treatment.

Effect of continuous compressive force on the expression of RANKL, OPG, and VEGF in osteocytes.

The present study aimed to investigate the effect of a compressive force (CF) on the expression of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), and vascular endothelial growth factor (VEGF) in murine osteocytes (MLO-Y4) as well as animal study. After application of a CF for 1, 3, 6, and 12 h, gene and protein expression of RANKL, OPG, and VEGF in MLO-Y4 cells were determined by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Furthermore, the effect of a stretch-activated (S-A) channel was examined by gadolinium (Gd3+) administration. In an animal experiment, the expression of these factors in osteocytes of alveolar bone was examined after experimental tooth movement in rats. After CF application, significant increases in RANKL, VEGF and RANKL/OPG ratio were shown. The upregulated gene and protein levels of these factors were reduced by Gd3+ administration. After tooth movement, upregulated RANKL and VEGF were imunohistochemically shown in osteocytes of alveolar bone. These findings suggest that CF application on osteocytes elevates expression of osteoclast-inducing factor and angiogenesis factor in vivo and vitro.

Mechanical load-induced H2S production by periodontal ligament stem cells activates M1 macrophages to promote bone remodeling and tooth movement via STAT1

BackgroundTooth movement is a unique bone remodeling process induced by mechanical stimulation. Macrophages are important in mediating inflammatory processes during mechanical load-induced tooth movement. However, how macrophages are regulated under mechanical stimulation remains unclear. Mesenchymal stem cells (MSCs) can modulate macrophage polarization during bone remodeling. Hydrogen sulfide (H2S) can be produced by MSCs and have been linked to bone homeostasis. Therefore, this study aimed to investigate whether H2S contributed to periodontal ligament stem cell (PDLSC)-regulated macrophage polarization and bone remodeling under mechanical stimulation.MethodsAn experimental mechanical load-induced tooth movement animal model was established. Changes in cystathionine-β-synthase (CBS), markers of M1/M2 macrophages, tooth movement distance, and the number of osteoclasts were examined. The conditioned medium of PDLSCs with or without mechanical loading was utilized to treat THP-1 derived macrophages for 24 h to further investigate the effect of PDLSCs on macrophage polarization. Different treatments with H2S donor, CBS inhibitor, or the inhibitor of STAT1 were used to investigate the related mechanism. Markers of M1/M2 polarization and STAT1 pathway expression were evaluated in macrophages.ResultsMechanical load promoted tooth movement and increased the number of M1-like macrophages, M1-associated pro-inflammatory cytokines, and the expression of CBS on the compression side of the periodontal ligament. The injection of CBS inhibitor or H2S donor could further repress or increase the number of M1-like macrophages, tartrate-resistant acid phosphatase-positive osteoclasts and the distance of tooth movement. Mechanistically, load-induced PDLSCs enhanced H2S production, which increased the expression of M1-associated cytokines in macrophages. These effects could be blocked by the administration of CBS inhibitor. Moreover, load-induced H2S steered M1 macrophage polarization via the STAT1 signaling pathway.ConclusionsThese data suggest a novel mechanism indicating that mechanical load-stimulated PDLSCs produce H2S to polarize macrophages toward the M1 phenotype via the STAT1 signaling pathway, which contributes to bone remodeling and tooth movement process. These results provide new insights into the role of PDLSCs in regulating macrophage polarization and mediating bone remodeling under mechanical stimulation, and indicate that appropriate H2S supplementation may accelerate tooth movement.

Evaluation of the effects of diode laser application on experimental orthodontic tooth movements in rats. Histopathological analysis.

Purpose:To evaluate the effect of diode laser use on experimental orthodontic tooth movements.Methods:Thirty Rattus norvegicus albinus Wistar were divided into three equal groups (n = 10), two experimentals and one control. Applying 20 g orthodontic force were attached to the maxillary incisors of the rats in all groups. Low dose laser was applied to the surrounding tissues of the maxillary incisors of the rats in the experimental groups. Two exposure times for laser irradiation were used for seven days: t = 12 min (energy dose = 72 J) and t = 9 min (energy dose = 54 J) by a 0.1 W DEKA brand diode laser with wavelength of 980 nm.Results:Osteoclastic activation increased in the 72 J group when compared to control group and decreased in comparison to the 54 J group. Osteoblastic activation was decreased in the 72 J group when compared to the control group and increased in comparison to the 54 J group.Conclusions:Applying 54 J laser energy has been found effective to accelerate the orthodontic tooth movement.

Effects of Glucocorticoids on Diurnal Variations in Experimental Tooth Movement

Effects of Glucocorticoids on Diurnal Variations in Experimental Tooth Movement

Evaluation of the effects of vitamins C and E on experimentalorthodontic tooth movement

Background. This experimental study aimed to assess the effects of Vitamins C and E on orthodontic tooth movement. Methods. Fifty-one male Wistar albino rats were divided into six groups: five appliance groups and one control group. The appliance groups had an orthodontic appliance consisting of a closed-coil spring ligated between the maxillary incisor and maxillary first molar (50 g). Vitamin E and C (150 mg/kg) were injected intraperitoneally per day in the first and second groups, respectively. Vitamins E and C (20 μL) were locally injected into the periodontal gap of the moving teeth in the third and fourth groups, respectively, once every three days. No vitamin was injected in the last (fifth) appliance group.The experimental period was 18 days. Histological and biochemical (alkaline phosphatase, osteocalcin, and NTx levels) evaluations of the samples were performed, and maxillary incisor‒molar distance was measured before and after the experiment. Results. The amount of tooth movement was similar in the appliance groups. All the vitamin groups showed significantly increased osteoblastic activity, while those treated with systemic vitamins exhibited significantly increased numbers of collagen fibers on the tension side compared to the appliance control group (P<0.05). Conclusion. Vitamin C and E supplements positively affected bone formation on the tension side of the teeth during experimental orthodontic tooth movement.

Hyalinization and Molecular Pathways Involved in Orthodontic Tooth Movement: A Systematic Review and Meta-Analysis

Objective: To systematically review the hyalinization of experimental tooth movement in humans and animals. Material and Methods: The electronic databases of MEDLINE, PubMed, Cochrane Library, Embase, Institute for Scientific Information, and Google Scholar were searched for performing a systematic review of the related literature published until 2019. Moreover, Endnote X9 software was utilized to manage electronic titles. The searches were fulfilled using keywords of “hyalinization,” “orthodontic tooth movement” OR “OTM” AND “periodontal ligament” OR “PDL,” “molecular pathways,” AND “mechanical cell.” Therefore, this systematic review was conducted based on the key consideration of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Forces ranged between 2.3 and 50 CN had been applied. According to the research design, incisors had been included in two experiments, whereas maxillary molars had been displaced by tipping forces in another rat examination. However, a majority of investigations had stated that hyalinization had firstly appeared within the first 24 hours. Moreover, the amount of prostaglandin-end peroxide synthase 2 (PTGS2) had been positively related to force term and size utilizing Western blotching. As PTGS2 had been included in the prostaglandin E2 (PGE2) metabolism, the up-regulation of PTGS2 gene expression could be connected with that of PGE2 emission. Conclusion: Gene expression in connection with force term and size and also the first signalling pathways were recognized utilizing protein-protein interactions (PPIs).

Low-intensity pulsed ultrasound enhances the rate of lateral tooth movement and compensatory bone formation in rats

Because mechanical stimulation of the periodontal ligament by low-intensity pulsed ultrasound (LIPUS) has been shown to increase the speed of bone remodeling, this study aimed to examine the effects of LIPUS stimulation on the rate of tooth movement and bone remodeling during lateral tooth movement. Twelve-week-old Wistar rats were divided into 2 groups. The LIPUS group received experimental tooth movement with LIPUS stimulation, and the tooth movement (TM) group were provided experimental tooth movement without LIPUS. For each group, the upper right first molars were moved buccally with fixed appliances. LIPUS exposure was placed in the region corresponding to the right maxillary first molar. Three days after tooth movement, tartrate-resistant acid phosphatase was examined. Fourteen days after tooth movement, the intermolar width, bone mineral content, and bone volume fraction were analyzed by micro-computed tomography, and newly formed bone was measured histomorphometrically. The number of TRAP-positive cells in the compressed region was higher in the LIPUS group. The intermolar width was significantly higher in the LIPUS group than in the TM group. The alveolar bone around the maxillary first molar showed no differences in bone mineral content and bone volume fraction between the LIPUS and TM groups. The LIPUS group exhibited a more significant amount of newly formed alveolar bone than the TM group. The present study provides evidence of the beneficial effects of LIPUS on the lateral tooth movement.

The central nucleus of the amygdala lesion attenuates orthodontic pain during experimental tooth movement in rats.

IntroductionOrthodontic pain is the most common adverse side effect reported in the context of tooth movement. Given its central role in processing pain and negative emotion, the central nucleus of the amygdala (CeA) is thought to be a key site involved in orthodontic pain sensation.MethodsIn the present study, we therefore explored whether the CeA is involved in contributing to orthodontic pain in a rat model of tooth movement. For this study, we utilized adult male rats with bilateral sham or electrolytic CeA lesions (400 μA; 25 s), and then we analyzed face grooming behavior as a measure of pain sensation.ResultsThrough this approach, we found that there were time‐ and force‐dependent factors influencing pain levels in these rats. We further found that bilateral CeA lesions markedly reduced tooth movement‐induced orofacial pain and that unilateral CeA lesions did so to a lesser extent.ConclusionsAs such, these results suggest the CeA is a key area of orthodontic pain, with the results of this study highlighting potential avenues for achieving pain relief in those suffering from orthodontic pain.

Vesicular nucleotide transporter mediates adenosine triphosphate release in compressed human periodontal ligament fibroblast cells and participates in tooth movement-induced nociception in rats

ObjectivePain control is imperative in orthodontic treatment. Adenosine triphosphate (ATP) is a key mediator released from periodontal ligament cells that excites nociceptive nerve endings. Vesicular nucleotide transporter (VNUT), encoded by the Solute carrier family 17 member 9 (SLC17A9) gene, participates in ATP uptake into secretory vesicles; thus, it may mediate tooth movement-induced pain. In the present study, we examined whether VNUT in periodontal ligament cells participates in tooth movement-induced nociception. DesignExpression levels of SLC17A9, connexin 43, and pannexin 1 in human periodontal ligament fibroblasts (HPDLFs) were examined by quantitative reverse transcription-polymerase chain reaction. Mechanical force via centrifugation-induced ATP release was measured using an ATP bioluminescence assay. Inhibitors were used to evaluate the role of ATP transporters. Face-grooming behaviors were assessed as indicators of nociceptive responses after experimental tooth movement in rats, as well as the effects of drugs for the pain-like behavior. ResultsAfter HPDLFs underwent mechanical stimulation by centrifugation, SLC17A9 mRNA expression in the cells was significantly upregulated. Increased ATP release from HPDLFs after mechanical stimulation was suppressed by treatment with clodronic acid, a VNUT inhibitor, at concentrations of 0.1 and 1.0 μM. In rats, face-grooming behaviors (indicators of nociception) were significantly increased on day 1 after experimental tooth movement. Increased face-grooming behaviors were suppressed by systemic administration of clodronic acid (0.1 mg/kg). ConclusionsThese results indicate that release of ATP from periodontal ligament cells via VNUT is important for nociceptive transduction during orthodontic treatment. Thus, VNUT may provide a novel drug target for tooth movement-induced pain.