Numerical simulation of orthodontic bone remodeling

Hypercementosis has been previously reported in mice lacking progressive ankylosis protein (Ank KO mice, or Ank, KO - knockout, WT - wildtype) due to decreased levels of the mineralization inhibitor inorganic pyrophosphate. However, the impact of hypercementosis on alveolar bone remodeling and periodontal ligament (PDL) maintenance from orthodontic forces during orthodontic tooth movement (OTM) remains unclear. To investigate the roles of ANK protein on tooth movement, PDL maintenance, alveolar bone remodeling, and tooth root resorption, we performed a split-mouth model of OTM induced by a closed-coil spring stretched between the maxillary first molar and maxillary incisors in Ank KO and WT mice (including both males and females). Micro-computed tomographic analysis revealed a 36.6% reduction in OTM in Ank KO mice compared with WT mice, although OTM-induced thickening of PDL was found to be similar in both groups. While reduced tissue mineral density (TMD) of the alveolar bone was observed in WT mice, TMD in Ank KO mice was maintained. Loss of Ank leads to wider roots with thicker cementum on the untreated, contralateral side, whereas a significant increase in OTM-induced root resorption was observed on the lateral tension side. Histologic analysis of root resorption confirmed these data and showed increased resorption lacunae located prevalently in the OTM tooth root cementum of Ank KO mice. Using a quantitative PCR array of bone-associated markers to interrogate total RNA harvested from PDL tissues along the root surface, we found alterations in gene expression from OTM in both WT and Ank KO mice, which included genes involved in bone remodeling, calciotropic hormones and receptors, cytokines, growth factors, and receptors. Our findings advance the understanding of the role of Ank in regulating mineralization in the periodontium as well as factors involved in root resorption.

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.

During orthodontic tooth movement, transcription factor hypoxia-inducible factor 1α (HIF1α) is stabilised in the periodontal ligament. While HIF1α in periodontal ligament fibroblasts can be stabilised by mechanical compression, in macrophages pressure application alone is not sufficient to stabilise HIF1α. The present study was conducted to investigate the role of myeloid HIF1α during orthodontic tooth movement. Orthodontic tooth movement was performed in wildtype and Hif1αΔmyel mice lacking HIF1α expression in myeloid cells. Subsequently, µCT images were obtained to determine periodontal bone loss, extent of orthodontic tooth movement and bone density. RNA was isolated from the periodontal ligament of the control side and the orthodontically treated side, and the expression of genes involved in bone remodelling was investigated. The extent of tooth movement was increased in Hif1αΔmyel mice. This may be due to the lower bone density of the Hif1αΔmyel mice. Deletion of myeloid Hif1α was associated with increased expression of Ctsk and Acp5, while both Rankl and its decoy receptor Opg were increased. HIF1α from myeloid cells thus appears to play a regulatory role in orthodontic tooth movement.

Many chemical messengers are involved in the process of alveolar bone and periodontal ligament remodelling during orthodontic tooth movement. Among them is probably endothelin-1 (ET-1). Its role in this process has been partly explained using tezosentan, which affects endothelin A (ET(A)) and endothelin B (ET(B)) receptors. Tezosentan enhances orthodontic tooth movement. The aim of this study was to determine the possible effects of a highly selective ET(A) antagonist on orthodontic tooth movement in rats. Thirty male Wistar rats, 11-12 weeks of age, divided into three equal groups. In group I, a closed-coil spring was used and they were treated daily with 15 mg/kg body weight of TBC3214, a highly selective ET(A) antagonist. A closed-coil spring was also used in group II and the animals were treated daily with a placebo. Group III were treated daily with a placebo. The coil spring delivered a force of 25 cN and was attached between the upper left first molar and upper left incisor. The distance between the teeth was measured with a digital calliper (accuracy +/- 0.01 mm) on days 0, 7, 14, 21, 24, 32, 37, and 40. The differences in the distance between the teeth were calculated to determine the amount of tooth movement. Statistical analysis was performed using two-way analysis of variance, Bonferroni's correction, and paired t-tests. The distance between the upper left first molar and the upper left incisor decreased in groups I and II. In group I, tooth movement was significantly less on days 32 and 37 (P < 0.01) and on day 40 (P < 0.001) compared with group II. In group III, the distance between the teeth increased during the study (P < 0.001). In animals treated daily with TBC3214, tooth movement was significantly less compared with the animals treated with a placebo. It is concluded that ET-1, which is the predominant form of endothelin isopeptides, is involved in orthodontic tooth movement in rats, probably by enhancing bone resorption via ET(A) receptors.

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.

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.

Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1β and vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor.

Exploring biological mechanisms in orthodontic tooth movement: Bridging the gap between basic research experiments and clinical applications – A comprehensive review

NiTi wires are considered as the most appropriate wires to be used during the initial phase of orthodontic treatment. This work presents anumerical method to simulate the coupling between the orthodontic appliance and bone remodeling, which are the two mechanisms responsible for the orthodontic tooth movement. The superelastic behavior of aNiTi wire was integrated in athree-dimensional simulation model to reproduce the long-term bone remodeling coupled with tooth alignment using the finite element method. The orthodontic load was derived by deforming the superelastic wire in order to adopt itself to the original position of irregular teeth. Root form was extracted from cone beam tomography imaging files. As aresult, the teeth were aligned while the wire was recovering its initial shape. The canine was intruded by 0.53 mm, while the neighboring teeth were extruded by 0.44 and 0.46 mm. When the wire was loaded, it generated aload of 4.6 N on the bracket bonded on the canine. This force was active during the first day of the treatment. Then, the force continued to decline until the end of the correction period. The decreasing load delivered from the wire affected the teeth displacements as observed in real situations. Despite the complexity of the presented numerical simulation, this procedure allowed the analysis of the orthodontic forces that were generated in the clinical experiments and of the biomechanical response of the periodontal support elements when using this kind of wire.

Human periodontal ligament (hPDL) fibroblasts are thought to receive mechanical stress (MS) produced by orthodontic tooth movement, thereby regulating alveolar bone remodeling. However, the role of intracellular calcium ([Ca2+]i)-based mechanotransduction is not fully understood. We explored the MS-induced [Ca2+]i responses both in isolated hPDL fibroblasts and in intact hPDL tissue and investigated its possible role in alveolar bone remodeling. hPDL fibroblasts were obtained from healthy donors’ premolars that had been extracted for orthodontic reasons. The oscillatory [Ca2+]i activity induced by static compressive force was measured by a live-cell Ca2+ imaging system and evaluated by several feature extraction method. The spatial pattern of cell-cell communication was investigated by Moran’s I, an index of spatial autocorrelation and the gap junction (GJ) inhibitor. The Ca2+-transporting ionophore A23187 was used to further investigate the role of [Ca2+]i up-regulation in hPDL cell behavior. hPDL fibroblasts displayed autonomous [Ca2+]i responses. Compressive MS activated this autonomous responsive behavior with an increased percentage of responsive cells both in vitro and ex vivo. The integration, variance, maximum amplitude, waveform length, and index J in the [Ca2+]i responses were also significantly increased, whereas the mean power frequency was attenuated in response to MS. The increased Moran’s I after MS indicated that MS might affect the pattern of cell-cell communication via GJs. Similar to the findings of MS-mediated regulation, the A23187-mediated [Ca2+]i uptake resulted in the up-regulation of receptor activator of NF-κB ligand (Rankl) and Sost along with increased sclerostin immunoreactivity, suggesting that [Ca2+]i signaling networks may be involved in bone remodeling. In addition, A23187-treated hPDL fibroblasts also showed the suppression of osteogenic differentiation and mineralization. Our findings suggest that augmented MS-mediated [Ca2+]i oscillations in hPDL fibroblasts enhance the production and release of bone regulatory signals via Rankl/Osteoprotegerin and the canonical Wnt/β-catenin pathway as an early process in tooth movement–initiated alveolar bone remodeling.—Ei Hsu Hlaing, E., Ishihara, Y., Wang, Z., Odagaki, N., Kamioka, H. Role of intracellular Ca2+–based mechanotransduction of human periodontal ligament fibroblasts.

Orthodontic movement is a continuous and balanced process characterized by resorption and apposition of bone in areas of pressure and tension after mechanical strength forces are applied. The purpose of this systematic review was to determine the effect of omega-3 administration on orthodontic tooth movement from various studies that have been carried out previously. Search articles online using PubMed, ProQuest, Scopus, Ebscohost, and Google Scholar between 1995-2021. The keywords used were (Orthodontic tooth movement OR Orthodontic movement AND bone remodelling OR Alveolar bone remodelling OR Alveolar remodelling AND Omega 3 OR Fatty acids OR EPA DHA). A total of 530 articles were obtained and then screened using titles, abstracts, and can access full text there are 44 articles. Then by using inclusion and exclusion criteria, three full-text journals were obtained and compiled using PRISMA. These studies show that omega-3 administration affects orthodontic tooth movement. Omega 3 can slow down the movement of orthodontic teeth so that it can consider as a method of preventing relapse by giving omega-3 at the end of orthodontic treatment.

Thinking Beyond the Wire: Emerging Biologic Relationships in Orthodontics and Periodontology

This study aimed to evaluate the effects of the estrogen depression during orthodontic tooth movement on alveolar bone microarchitecture and periodontal ligament. Female Wistar rats were divided into two groups, one consisting of non-ovariectomized animals subjected to orthodontic tooth movement, and one comprising ovariectomized animals subjected to orthodontic tooth movement. Micro-CT assessment of bone volume to total volume (BV/TV), total porosity, trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) in the alveolar bone of the orthodontically moved tooth was performed. Histomorphometric analyses were made in the periodontal ligament, and immunoexpression of RANK, RANKL, OPG, and TUNEL were quantified. Orthodontic tooth movement in the group of ovariectomized rats was faster than in non-ovariectomized animals. The alveolar bone area showed lower values of BV/TV and trabecular thickness, and higher bone porosity and trabeculae numbers in the ovariectomized rats. Histological analyses in the ovariectomized group revealed an increase in collagen fibers in the periodontal ligament. The apoptotic cell counts in the periodontal ligament were higher in the group of ovariectomized rats than in the sham-operated rats. Ovariectomy resulted in an increase in tooth movement and alteration of the alveolar bone microstructure in the first 7day of orthodontic tooth movement, and in the presence of apoptotic cells in the periodontal ligament.

Introduction With an increasing demand for orthodontic treatment for adult patients, orthodontic professionals are constantly seeking novel strategies and technologies that can accelerate tooth movement in order to shorten the treatment period. For instance, in recent years, the influences of different surgical techniques on orthodontic tooth movement in the ipsilateral side of surgery were intensively investigated. Here, we attempt to examine if corticotomy could also affect the rate of tooth movement in the contralateral side of the surgery by using a rodent model. Materials and Methods 72 eight-week-old Sprague-Dawley rats were randomly divided into three groups as follows: the Control group (orthodontic treatment devices delivered only, no tooth movement), the orthodontic tooth movement (OTM) group (orthodontic treatment devices delivered and orthodontic treatment performed), and the Corticotomy + OTM group (remote corticotomy performed, orthodontic treatment devices delivered, followed by orthodontic treatment). The surgical procedure was conducted on the right side of the maxilla at the time of appliance placement and a force of 60 g was applied between the maxillary left first molar and maxillary incisors using nickel-titanium springs to stimulate OTM. The OTM distance and speed were tracked at 3, 7, 14, and 28 days post-surgery, followed by histological and immunohistochemical assessments. Results In comparison with orthodontic treatment only, the contralateral corticotomy significantly accelerated OTM. Furthermore, animals undergoing corticotomy + OTM presented with a greater number of osteoclasts on the compression side, stronger staining of the osteogenic marker on the tension side, and higher expression of an inflammatory marker than the OTM group animals. Conclusion Our current study demonstrates that remote corticotomy effectively accelerates alveolar bone remodeling and OTM. The study enriches our understanding of the regional acceleratory phenomenon (RAP) and offers an alternative strategy for accelerating OTM to shorten the orthodontic treatment period.

PurposeMany adult orthodontic patients suffer from periodontitis, which is caused by oral pathogens such as the gram-negative Aggregatibacter actinomycetemcomitans (Agac). Like orthodontic tooth movement, periodontitis is associated with inflammation and alveolar bone remodelling thereby affecting orthodontic treatment. Interactions of both processes, however, are not sufficiently explored, particularly with regard to oxidative stress.MethodsAfter preincubation with Agac lysate for 24 h periodontal ligament fibroblasts (PDLF) were either stretched or compressed for further 48 h simulating orthodontic forces in vitro. We analysed the expression of genes and proteins involved in the formation of reactive oxygen species (NOX-4, ROS) and nitric oxide (NOS-2), inflammation (TNF, IL-6, PTGS-2) and bone remodelling (OPG, RANKL).ResultsAgac lysate elevated the expression of NOX-4, NOS-2, inflammatory IL-6 and PTGS-2 and the bone-remodelling RANKL/OPG ratio during compressive, but not tensile mechanical strain. Agac lysate stimulated pressure-induced inflammatory signalling, whereas surprisingly ROS formation was reduced. Pressure-induced downregulation of OPG expression was inhibited by Agac lysate.ConclusionsAgac lysate impact on the expression of genes and proteins involved in inflammation and bone remodelling as well as ROS formation, when PDLF were subjected to mechanical forces occurring during orthodontic tooth movement.