Reduced orthodontic tooth movement in Ank knockout mice.

BackgroundThe aim of this study was to dynamically evaluate tooth movement, root resorption, and remodeling of alveolar bone using different forces to cause tooth movement in rats.Material/Methods12-week-old male Sprague-Dawley rats were selected. Nickel-titanium (Ni-Ti) coil springs (20 g, 50 g, and 100 g forces) were placed for mesial movement of the left first maxillary molar teeth. Tooth movement, root resorption, and microarchitectural parameters of the trabecular bone were evaluated by in vivo micro-CT. Histological examination was used to observe the root resorption, alveolar bone remodeling, and changes in osteoclasts from day 0 to day 14.ResultsThe tooth movement distance increased significantly over the initial 3 days in the 3 groups. The 20 g force group showed more tooth movement than in the 50 and 100 g force groups after 14 days (P<0.05). From days 7 to 10, root resorption lacunae appeared in the 3 groups and then stabilized, and the 100 g force group produced more lacunar resorption than in the anther 2 groups (P<0.05). Compared to day 0, the trabecular thickness and bone volume fraction on the pressure side gradually decreased from day 7 to day 14. The structure model index increased significantly from day 3 to day 14. Histological examination showed remarkable root resorption craters and osteoclasts positive for tartrate-resistant acid phosphatase in the root resorption lacunae in the 50 g and 100 g groups from day 7 to day 14.ConclusionsA 100 g heavy force can be used to establish a root resorption model in rats.

This study aims to investigate whether cumulative dose-dependent isotretinoin (Roaccutane®) could affect orthodontic tooth movement (OTM) and root resorption. Ninety male Wistar Albino rats were divided into 4 groups. While, the control (SALINE), solvent (SOYBEAN) and orthodontic drug (ISOTM) groups underwent orthodontic force, the non-orthodontic drug group (ISO) did not. The rats were administrated saline, soybean oil (SBO) and isotretinoin diluted in SBO (ISOTM, ISO) for 30 days, respectively. Six rats were euthanized in each orthodontic group. Fifty grams of orthodontic force was applied to the remaining rats' first molars using the incisors as anchorage. Six more rats in each group were euthanized on the 7th, 14th and 21st days of the force application. In the ISO group, six rats were euthanized on the 37th, 44th and 51st days of administration. Six rats that were euthanized for ISOTM on the 30th day were also used for ISO to reduce the number of rats used. Micro-computed tomography (micro-CT) and histological analysis were performed. Independent of orthodontic force, isotretinoin caused root resorption in the apical region. However, there was no statistically significant influence of isotretinoin on OTM and orthodontically induced root resorption (OIRR). Despite the lack of strong evidence supporting the orthodontically induced resorptive effect of isotretinoin, this study provided findings regarding the resorptive effects of isotretinoin on non-orthodontic root resorption. Therefore, the present results underscore the importance of close monitoring during orthodontic treatment to mitigate potential root resorption in patients who use isotretinoin because of acne complaints.

Vitamin A is essential not only for bone metabolism and development but also for the normal functioning of many physiological processes in the body. Despite vitamin A's important involvement in bone metabolism, its effect on orthodontic tooth movement is not entirely known. Previous studies on animals have suggested that vitamin A may influence alveolar bone remodelling and tooth movement, but the effect of various doses of vitamin A on these processes remains poorly understood. This experiment was designed to examine the effect of vitamin A on the orthodontic tooth movement of male rats. Eighty male rats weighing 200-250 grams were divided into eight equal parallel groups. An initial orthodontic force was applied to all groups with a specific appliance, and six different doses of vitamin A were administered (250-2500 IU/Kg intraperitoneally). Two control groups were also considered. Orthodontic tooth movement was measured at the beginning and end of the study period (day 14), and serum alkaline phosphatase (ALP) level was evaluated. The maxillary sections were also evaluated by histological examination. Although there was a dose-dependent increase in tooth movement observed with vitamin A administration, the differences were not statistically significant. There was no significant difference in the number of osteoclasts or the presence of lacunae on the root surface between the study groups. Root resorption was observed in different areas of the root and was not related to different doses of vitamin A. The serum ALP level did not show any significant difference between the groups treated with different doses of vitamin A. Despite the known effects of vitamin A on bone metabolism, the results of this study suggest that vitamin A did not increase alveolar bone remodeling and orthodontic tooth movement in male rats.

BackgroundOrthodontic tooth movement (OTM) is a complex biological process triggered by orthodontic forces (OF). This study aims to study the influence of sex and age on the gene expression of the dental pulp (DP) and periodontal ligament (PDL) of human premolars subjected to 7 and 28 days of OF in vivo.MethodologyLinear mixed and negative-binomial models were used on previously published RNA sequencing (RNA-seq) datasets of DP and PDL tissue subjected to OF for 7 days and 28 days to verify if the effect of OF depends on sex and age. Differentially expressed genes (DEGs) were identified using false discovery rate and functional analysis was performed.ResultsThe datasets consisted of 69 DP and 63 PDL samples from 46 and 41 patients respectively, with similar sex and age distribution. RNA-seq showed that sex did not influence the DP’s gene expression profile, since only one DEG related to immune response was detected after 28-days of OF. In contrast, sex significantly affected PDL: 505 DEGs were found after 7 days of OF, related to bone homeostasis, osteoclastic activity and immune response. Age impacted both tissues; in DP, 18 DEGs related to Ca2⁺ regulation and DNA damage repair were found at 7 days, and 10 DEGs associated with repair and adaptive capacities emerged at 28 days. In PDL, 181 genes related to bone regeneration were identified at 28 days, with no DEGs noted at 7 days.ConclusionOur study demonstrates that under OF, DP’s reaction is not sex-based, whereas PDL’s is, particularly in the early phase of OTM, with women showing a more pronounced osteoclastic response. Age-related effects in DP tissue primarily influence Ca2+ homeostasis and DNA damage repair in early phases, and tissue repair and adaptive responses later. In contrast, age impacts PDL tissue mainly in the later stages of OTM, affecting its regenerative capacity.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40510-025-00596-w.

Many patients regularly take histamine receptor antagonists, such as cetirizine, to prevent allergic reactions, but these antiallergic drugs may have inadvertent effects on orthodontic treatment. In previous studies, histamine has been shown to modulate the sterile inflammatory reaction underlying orthodontic tooth movement. Pertinent effects of histamine antagonization via cetirizine during orthodontic treatment, however, have not been adequately investigated. We thus treated male Fischer344 rats either with tap water (control group) or cetirizine by daily oral gavage corresponding to the clinically used human dosage adjusted to the rat metabolism (0.87 mg/kg) or to a previously published high dosage of cetirizine (3 mg/kg). Experimental anterior movement of the first upper left molar was induced by insertion of a nickel-titanium (NiTi) coil spring (0.25 N) between the molar and the upper incisors. Cone-beam computed tomography (CBCT), micro-computed tomography (µCT) images, as well as histological hematoxylin-eosin (HE), and tartrate-resistant acid phosphatase (TRAP) stainings were used to assess the extent of tooth movement, cranial growth, periodontal bone loss, root resorptions, and osteoclast activity in the periodontal ligament. Both investigated cetirizine dosages had no impact on the weight gain of the animals and, thus, animal welfare. Neither the extent of tooth movement, nor cranial growth, nor root resorption, nor periodontal bone loss were significantly influenced by the cetirizine dosages investigated. We, thus, conclude that histamine receptor antagonist cetirizine can be used during orthodontic treatment to prevent allergic reactions without clinically relevant side effects on orthodontic tooth movement.

Numerical simulation of orthodontic bone remodeling

Antidepressant drugs such as fluoxetine are of the most commonly used drugs among the public. These drugs may impact the regulation of bone cell functioning, and thus affect orthodontic tooth movement. The aim of this study was to determine the effect of fluoxetine on tooth movements during orthodontic treatment in rats. In this study, 30 male rats were randomly assigned into two groups and injected with fluoxetine 10 mg/kg (experimental group) and normal saline (control group) for a period of 1-month intraperitoneally 5 times/week. Then, the rats were anesthetized and a nickel-titanium closed-coil spring was placed between the left maxillary first molar and left maxillary central incisors of all samples, and then fluoxetine (experimental group) and normal saline (control group) were injected for another 3 weeks by the same method. After measuring tooth movements, rats were sacrificed, and histomorphometric analyses were conducted and the obtained data were statistically analyzed using independent t-test and the significance was set at 0.05. Following the fluoxetine injection, the mean amount of tooth movements in the experimental group was reduced compared to the control group, which was not statistically significant (P = 0.14). There was no significant difference between the two groups regarding bone apposition rate (P = 0.83), external root resorption rate (P = 0.1), and mean number of root resorption lacunae (P = 0.16). Within the limitations of this study, systemic use of fluoxetine may cause insignificant reduction of tooth movement rate in rats; however, this subject needs more evaluations.

The aim of this study was to examine the effect of methylphenidate, prescribed for individuals with attention deficit hyperactivity disorder (ADHD), on orthodontic tooth movement (OTM) and root resorption. In all, 30 rats were divided into(1) control(C), (2) constant (MCD), and (3) increasing dose of methylphenidate (MID) groups and 2subgroups for each of them (nonorthodontic (30days)/orthodontic (44days)). After receiving saline or methylphenidate for 30days, rats in the nonorthodontic groups were euthanized (n = 5/group). Subsequently, 50 g of orthodontic force was applied to the remaining rats' first molars for 14days (orthodontic groups). Quantitative micro-computed tomography (micro-CT) and immunohistochemical analyses were conducted. For statistical analyses Kruskal-Wallis and Dunnet tests were applied with asignificance set at p < 0.05. Micro-CT analysis demonstrated astatistically significant increase in tooth displacement with higher doses of methylphenidate compared to control and lower-dose groups, though no significant difference was detected between MID-44 and MCD-44groups. Orthodontic force led to asignificant increase in root resorption, peaking in the coronal region and diminishing toward the apex. The highest amount of resorption was observed in the MID groups, with asignificant difference between nonorthodontic MID-30 and C‑30groups. No significant changes in bone parameters were noted in the tension zone, but numerical reductions in trabecular thickness (Tb.Th), bone volume fraction (BV/TV), and bone mineral density (BMD) were observed. In nonorthodontic cohorts, VEGF and RANK levels were significantly elevated in the MID-30 group, along with increased TRAP expression, indicating bone resorption. Orthodontic cohorts exhibited asignificant increase in RANK- and TRAP-positive cells with methylphenidate administration. Reductions in OPG and elevations in RANK, RANKL, VEGF, and TRAP were noted, primarily between orthodontic and nonorthodontic groups. The present rat model suggests aweak potential for methylphenidate to increase root resorption. However, increased doses of methylphenidate accelerated OTM.

Runx1/miR-26a/Jagged1 signaling axis controls osteoclastogenesis and alleviates orthodontically induced inflammatory root resorption

Background: Bone remodeling and metabolism associated with orthodontic tooth movement are regulated by a large number of local and systemic factors. The widespread useof therapeutic corticosteroids (GCs) today raise concerns with regard to their effects on mineralized tissue metabolism. This study aimed to investigate the effect of Methylprednisolone treatment on alveolar bone remodeling during orthodontic tooth movement. Materials and Methods: A twenty-six 12-weeks old male Wistar albino rats were divided into 2 groups; control group (n = 13) without any drug administration during the study and steroidal group (n = 13) which received 5 mg/kg/day of methylprednisolone for 3 weeks. A split- mouth design was used performing orthodontic tooth movement on the upper right 1st molar by applying 20 g of mesial force using superelastic closed-coil spring attached to the incisors for 21 days while the upper left side served as the non-appliance side. Orthodontic tooth movement was evaluated on weekly basis using digital caliber. The rats were sacrificed after 3 weeks and alveolar bone remodeling process was evaluated by counting the number of osteoblast and osteoclast cells at the compression and tension sites at the coronal and apical levels of the mesiobuccal root of upper 1st molar in both appliance and non-appliance sides using digital microscope at 400× magnification. At day of sacrifice serum measurements for alkaline phosphatase (ALP) and acid phosphatase (ACP) activity were carried out. Results: Showed that in the steroid group there was significantly greater amount of orthodontic tooth movement, greater reduction of bone formation and an increase in bone resorption with the presence of orthodontic appliance, increase in serum ACP activity and reduction of serum ALP activity as compared with the control group,(P ≤ 0.05). Conclusion: The Methylprednisolone therapy in low-medium doses elicits a noticeable change in the bone turnover rate during orthodontic tooth movement.

To compare inflammatory cytokine and defensin expression in response to experimental dry eye (EDE) in interleukin-1 receptor-1 (IL-1R1)-deficient (KO) mice with age-matched wild-type mice (WT). EDE was induced by subcutaneous scopolamine injection, exposure to low humidity, and an air draft for 5 days in 4- to 6-week-old KO and WT mice. Expression of cytokines IL-1 alpha, IL-1 beta, tumor necrosis factor (TNF)-alpha, IL-6, and mouse beta-defensins (mBD)-1, mBD-2, and mBD-3 was evaluated by real-time polymerase chain reaction in scraped corneal epithelial cells and whole conjunctival tissues. A multiplex bead assay was performed to quantitate IL-1 alpha, IL-2, IL-4, IL-10, interferon (IFN)-gamma, and TNF-alpha levels in tear fluid, and an enzyme immunoassay was used to quantitate IL-1 beta levels in tear fluid. EDE significantly increased RNA transcripts for IL-1 alpha and beta in the conjunctiva and for TNF-alpha in the corneal epithelium of WT mice. Levels of IL-1 alpha, IL-1 beta, and IL-6 were significantly lower in the corneal epithelium and conjunctiva, and TNF-alpha was significantly lower in the cornea of KO mice after 5 days of EDE than WT mice. Tear fluid IL-1 alpha concentration increased above baseline on days 2-4 of EDE in WT and KO mice. A similar pattern was observed for tear TNF-alpha. Tear IL-1 beta increased throughout the 5 days of EDE in WT and KO mice. IFN-gamma, IL-2, IL-4, and IL-10 were undetectable in tear fluid of either strain before or after EDE. Corneal mBD-1 mRNA expression was unchanged and conjunctival mBD-1 transcripts decreased in WT and increased in KO mice with EDE. Untreated WT corneas, but not those of KO mice, expressed mBD-2 transcripts, whereas in the conjunctiva, mBD-2 increased in WT and decreased in KO mice with EDE. Corneal mBD-3 mRNA expression was undetected in WT mice, but increased after EDE in KO mice. Conjunctival mBD-3 transcripts were only detected in WT with EDE. These findings indicate that IL-1 signaling is responsible in part for the increased expression of inflammatory cytokines and the changes in mBDs by the ocular surface tissues in response to desiccating stress. These results show the important regulatory aspects of IL-1 on ocular surface epithelial inflammation.

ABSTRACTIntroduction: Osteoclasts and osteoblasts are responsible for regulating bone homeostasis during which the trace element zinc has been shown to exert a cumulative effect on bone mass by stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption. Objective: The aim of the present study was to investigate the effects of zinc (Zn) on orthodontic tooth movement (OTM) in a rat model. Material and Methods: A total of 44 male Wistar rats were divided into four groups of 11 animals each and received 0, 1.5, 20 and 50 ppm Zn in distilled water for 60 days. In the last 21 days of the study, nickel-titanium closed coil springs were ligated between maxillary right incisors and first molars of all rats, and tooth movement was measured at the end of this period. Histological analysis of hematoxylin/eosin slides was performed to assess root resorption lacunae, osteoclast number and periodontal ligament (PDL) width. Results: Mean OTM was calculated as 51.8, 49.1, 35.5 and 45 µm in the 0, 1.5, 20 and 50 ppm zinc-receiving groups, respectively. There were no significant differences in neither OTM nor histological parameters among the study groups (p > 0.05). Conclusion: According to the results obtained in the current investigation, increase in supplementary zinc up to 50 ppm does not affect the rate of OTM neither bone and root resorption in rats.

During orthodontic tooth movement (OTM) a remodeling of the periodontal ligament (PDL) and the alveolar bone occurs. We have recently observed that the expression of CGRP and substance P (SP) increases in the PDL and dental pulp in response to buccally directed OTM of the upper first molar in the rat. We have now examined whether there is also an involvement of VIP and NPY in this type of OTM. A sectional arch wire cemented to the upper incisors exerted an orthodontic force, mediated by a coil on the lingual side of the tooth, for 24 hours. It was observed that the blood vessels in the periodontal ligament were supplied with VIP- and NPY-immunoreactive (IR) nerve fibers, whereas VIP-IR nerve fibers in contrast to NPY-IR fibers were only occasionally observed in the dental pulp. No significant changes were observed in response to OTM. The observations suggest that VIP and NPY, in contrast to the main sensory neuropeptides CGRP and SP, are not involved in the tissue processes that occur in the remodeling of PDL and alveolar bone during orthodontic tooth movement.

Due to the overwhelming desire among adults for shorter orthodontic treatment times, there is a growing trend in research that focuses on accelerating procedures for tooth movement. Unfortunately, lengthy orthodontic treatment times come with a number of adverse effects, including an increased risk of tooth decay, gingival recession, and root resorption. Finding the greatest way to maximize tooth motion with the least drawbacks is now more important than ever. The surgical method provides the most dependable results, but its invasiveness limits its use. Corticotomy is one of the commonly used techniques in practice for acceleration of orthodontic tooth movement. Numerous corticotomy methods have been successful in causing accelerated tooth movement. Through the use of these approaches, local acceleratory phenomena are activated, fostering an ideal milieu for tooth movement acceleration. In order to expedite orthodontic tooth movement while adhering to a specified surgical and orthodontic regimen, the piezocision treatment appears to be the ideal compromise. In cases of dehiscence and/or fenestration on the alveolar bone linked to moderate to severe overcrowding, piezocision surgery enables the inclusion of biomaterials. Low-level laser therapy and orthognathic surgery-first are also methods used to accelerate tooth motion among various others. However, further research should be done to ascertain the optimal way to accelerate tooth movement because each approach has benefits and drawbacks. The purpose of this research is to review the available information about methods and technology used to accelerate dental movements in orthodontic treatments..

Background: This study aimed to evaluate the stress distributions in the periodontal ligament (PDL) and alveolar bone of immature maxillary central incisors with regenerative endodontic treatment (RET) and natural immature teeth under different orthodontic forces using three-dimensional finite element analysis (FEA). Methods: 3D models of natural immature and RET-treated central incisors were created using SolidWorks software. In the RET model, a 3 mm MTA plug was added to the canal, and a regenerative tissue simulation was added to the pulp cavity. Dentin, PDL, and bone were considered homogeneous, isotropic, and linear elastic. Tetrahedral meshing and convergence analysis were performed. Three different loading scenarios of 1 N were applied from the bracket level: mesial translation, mesio-buccal rotation, and palatal tilt. Maximum principal tensile and compressive stresses were calculated in PDL and bone. Results: Similar maximum tensile stress values (0.110–0.151 MPa) were found in both natural and RET-treated teeth under all loading scenarios. Stresses were concentrated in the crestal regions of the PDL and corresponding bone areas. In RET models, stress in the PDL was more widely and homogeneously distributed, while bone stress patterns remained largely similar between models. Conclusion: RET-treated immature teeth exhibit similar stress distribution to natural teeth under orthodontic forces. These results support that light and controlled forces can be safely used on RET-treated teeth; however, long-term follow-up studies are required for clinical confirmation. Keywords: Finite Element Analysis; Orthodontic Tooth Movement; Regenerative Endodontics; Periodontal Ligament.