The Biomechanical Function of Periodontal Ligament Fibres in Orthodontic Tooth Movement

Orthodontic tooth movement occurs as a result of resorption and formation of the alveolar bone due to an applied load, but the stimulus responsible for triggering orthodontic tooth movement remains the subject of debate. It has been suggested that the periodontal ligament (PDL) plays a key role. However, the mechanical function of the PDL in orthodontic tooth movement is not well understood as most mechanical models of the PDL to date have ignored the fibrous structure of the PDL. In this study we use finite element (FE) analysis to investigate the strains in the alveolar bone due to occlusal and orthodontic loads when PDL is modelled as a fibrous structure as compared to modelling PDL as a layer of solid material. The results show that the tension-only nature of the fibres essentially suspends the tooth in the tooth socket and their inclusion in FE models makes a significant difference to both the magnitude and distribution of strains produced in the surrounding bone. The results indicate that the PDL fibres have a very important role in load transfer between the teeth and alveolar bone and should be considered in FE studies investigating the biomechanics of orthodontic tooth movement.     

Experimental model of tooth mobility in the human "in vivo"]

The aim of the present study was to investigate experimentally the mechanical properties of tooth deflection under external loading. These properties have a significant impact on tooth movement during orthodontic treatment. The stresses and strains caused by tooth movement influence bone remodelling, which is the basis of orthodontic treatment. The movement of a tooth as a direct reaction to the forces acting on it is termed "initial" movement. It is nonlinear and has a clearly time-dependent component. While the initial tooth movement represents the totality of the reaction mechanisms of all the tissues of the tooth unit, it is determined primarily by the mechanical properties of the periodontal ligament (PDL). The PDL is the softest tissue of the tooth unit and is therefore subject to the largest deformations when forces act on the crown of the tooth. The objective of orthodontic treatment is to achieve as precise and rapid tooth movement as possible, without provoking such undesired effects as bone and root resorption. To enable the implementation of an optimal orthodontic force system that meets these requirements, a thorough knowledge of the biomechanics of tooth movement is a must.     

A mechanobiological model of orthodontic tooth movement

Orthodontic tooth movement is achieved by the process of repeated alveolar bone resorption on the pressure side and new bone formation on the tension side. In order to optimize orthodontic treatment, it is important to identify and study the biological processes involved. This article presents a mechanobiological model using partial differential equations to describe cell densities, growth factor concentrations, and matrix densities occurring during orthodontic tooth movement. We hypothesize that such a model can predict tooth movement based on the mechanobiological activity of cells in the PDL. The developed model consists of nine coupled non-linear partial differential equations, and two distinct signaling pathways were modeled: the RANKL–RANK–OPG pathway regulating the communication between osteoblasts and osteoclasts and the TGF-β pathway mediating the differentiation of mesenchymal stem cells into osteoblasts. The predicted concentrations and densities were qualitatively validated by comparing the results to experiments reported in the literature. In the current form, the model supports our hypothesis, as it is capable of conceptually simulating important features of the biological interactions in the alveolar bone—PDL complex during orthodontic tooth movement.     

正畸牙移动相关信号通路研究进展

<正>畸牙移动是在机械力的作用下,通过对牙周膜产生牵张或压缩的力来引起牙周组织在生理限度内的组织改建,从而达到牙齿移动、矫治畸形的目的。由于没有明显的年龄限制,正畸矫治在全球范围已变得越来越普遍。因此,相关的研究也日益增多。牙齿移动的生物学基础是正畸力作用于牙周组织激活一系列信号转导通路,进而引起牙周膜的修复改建。为指导临床、加速正畸矫治疗程提供新的思路,本文综述了近年来有关正畸牙移动相关信号通路的研究进展。发现最新的研究集中在MAPK信号通路,Wnt/β-catenin信号通路,PI3K/AKt/m TOR信号通路,BMP-2信号通路,Caspase-3介导的凋亡通路较多。但是正畸牙移动引起的牙周组织改建是一个多种生物力学信号转导通路相互调节相互作用的过程,对于上述信号通路之间的相互关系还有待于我们更进一步的探索。     

Mass acquisition of human periodontal ligament stem cells

The periodontal ligament (PDL) is an essential fibrous tissue for tooth retention in the alveolar bone socket. PDL tissue further functions to cushion occlusal force, maintain alveolar bone height, allow orthodontic tooth movement, and connect tooth roots with bone. Severe periodontitis, deep caries, and trauma cause irreversible damage to this tissue, eventually leading to tooth loss through the destruction of tooth retention. Many patients suffer from these diseases worldwide, and its prevalence increases with age. To address this issue, regenerative medicine for damaged PDL tissue as well as the surrounding tissues has been extensively investigated regarding the potential and effectiveness of stem cells, scaffolds, and cytokines as well as their combined applications. In particular, PDL stem cells (PDLSCs) have been well studied. In this review, I discuss comprehensive studies on PDLSCs performed in vivo and contemporary reports focusing on the acquisition of large numbers of PDLSCs for therapeutic applications because of the very small number of PDLSCs available in vivo.     

Low-Intensity Pulsed Ultrasound Accelerates Tooth Movement via Activation of the BMP-2 Signaling Pathway

The present study was designed to determine the underlying mechanism of low-intensity pulsed ultrasound (LIPUS) induced alveolar bone remodeling and the role of BMP-2 expression in a rat orthodontic tooth movement model. Orthodontic appliances were placed between the homonymy upper first molars and the upper central incisors in rats under general anesthesia, followed by daily 20-min LIPUS or sham LIPUS treatment beginning at day 0. Tooth movement distances and molecular changes were evaluated at each observation point. In vitro and in vivo studies were conducted to detect HGF (Hepatocyte growth factor)/Runx2/BMP-2 signaling pathways and receptor activator of NFκB ligand (RANKL) expression by quantitative real time PCR (qRT-PCR), Western blot and immunohistochemistry. At day 3, LIPUS had no effect on the rat orthodontic tooth movement distance and BMP-2-induced alveolar bone remodeling. However, beginning at day 5 and for the following time points, LIPUS significantly increased orthodontic tooth movement distance and BMP-2 signaling pathway and RANKL expression compared with the control group. The qRT-PCR and Western blot data in vitro and in vivo to study BMP-2 expression were consistent with the immunohistochemistry observations. The present study demonstrates that LIPUS promotes alveolar bone remodeling by stimulating the HGF/Runx2/BMP-2 signaling pathway and RANKL expression in a rat orthodontic tooth movement model, and LIPUS increased BMP-2 expression via Runx2 regulation.     

Strain-dependent up-regulation of ephrin-B2 protein in periodontal ligament fibroblasts contributes to osteogenesis during tooth movement

During orthodontic tooth movement, the application of adequate orthodontic forces allows teeth to be moved through the alveolar bone. These forces are transmitted through the periodontal ligaments (PDL) to the supporting alveolar bone and lead to deposition or resorption of bone, depending on whether the tissues are exposed to a tensile or compressive mechanical strain. Fibroblasts within the PDL (PDLF) are considered to be mechanoresponsive. The transduction mechanisms from mechanical loading of the PDLF to the initiation of bone remodeling are not clearly understood. Recently, members of the ephrin/Eph family have been shown to be involved in the regulation of bone homeostasis. For the first time, we demonstrate that PDLF exposed to tensile strain induce the expression of ephrin-B2 via a FAK-, Ras-, ERK1/2-, and SP1-dependent pathway. Osteoblasts of the alveolar bone stimulated with ephrin-B2 increased their osteoblastogenic gene expression and showed functional signs of osteoblastic differentiation. In a physiological setting, ephrin-B2-EphB4 signaling between PDLF and osteoblasts of the alveolar bone might contribute to osteogenesis at tension sites during orthodontic tooth movement.     

Quantitative approach for the prediction of tooth movement during orthodontic treatment

The orthodontic treatment is aimed to displace and/or rotate the teeth to obtain the functionally correct occlusion and the best aesthetics and consists in applying forces and/or couples to tooth crowns. The applied loads are generated by the elastic recovery of metallic wires linked to the tooth crowns by brackets. These loads generate a stress state into the periodontal ligament and hence, in the alveolar bone, causing the bone remodeling responsible for the tooth movement. The orthodontic appliance is usually designed on the basis of the clinical experience of the orthodontist. In this work, a quantitative approach for the prediction of the tooth movement is presented that has been developed as a first step to build up a computer tool to aid the orthodontist in designing the orthodontic appliance. The model calculates the tooth movement through time with respect to a fixed Cartesian frame located in the middle of the dental arch. The user interface panel has been designed to allow the orthodontist to manage the standard geometrical references and parameters usually adopted to design the treatment. Simulations of specific cases are reported for which the parameters of the model are selected in order to reproduce forecasts of tooth movement matching data published in experimental works.     

Quantitative Approach for the Prediction of Tooth Movement During Orthodontic Treatment

The orthodontic treatment is aimed to displace and/or rotate the teeth to obtain the functionally correct occlusion and the best aesthetics and consists in applying forces and/or couples to tooth crowns. The applied loads are generated by the elastic recovery of metallic wires linked to the tooth crowns by brackets. These loads generate a stress state into the periodontal ligament and hence, in the alveolar bone, causing the bone remodeling responsible for the tooth movement. The orthodontic appliance is usually designed on the basis of the clinical experience of the orthodontist. In this work, a quantitative approach for the prediction of the tooth movement is presented that has been developed as a first step to build up a computer tool to aid the orthodontist in designing the orthodontic appliance. The model calculates the tooth movement through time with respect to a fixed Cartesian frame located in the middle of the dental arch. The user interface panel has been designed to allow the orthodontist to manage the standard geometrical references and parameters usually adopted to design the treatment. Simulations of specific cases are reported for which the parameters of the model are selected in order to reproduce forecasts of tooth movement matching data published in experimental works.     

Interdental distraction osteogenesis and rapid orthodontic tooth movement: a novel approach to approximate a wide alveolar cleft or bony defect

The closure of a wide alveolar cleft and fistula in cleft patients and the reconstruction of a maxillary dentoalveolar defect in traumatic patients are challenging for both orthodontists and surgeons. This is due to the difficulty in achieving complete closure by using local attached gingiva and the great volume of bone required for the graft. In this article, the authors propose using interdental distraction osteogenesis to create a segment of new alveolar bone and attached gingiva for the complete approximation of a wide alveolar cleft/fistula and the reconstruction of a maxillary dentoalveolar defect. They performed this procedure on one patient with a traumatic maxillary dentoalveolar defect and 10 patients with unilateral or bilateral cleft lips and palates who had varied dentoalveolar clefts/fistulas. Interdental and maxillary osteotomies were performed on one side of the dental arch by the cleft or defect. After a latency period of 3 days, the osteotomized distal segment of the dental arch was then distracted and transported toward the cleft or defect by using a toothborne intraoral distraction device. The alveoli and gingivae on both ends of the cleft or defect were approximated after distraction osteogenesis. The need for extensive alveolar bone grafting was eliminated. A segment of new edentulous alveolus and attached gingiva was created interdentally at a site distant to the cleft or defect. In the cleft patients, teeth were moved orthodontically into the regenerate (newly formed alveolar bone) dental crowding 1 week after distraction. The orthodontic tooth movement was rapidly completed in 3 months, and the edentulous space was eliminated. Interdental distraction osteogenesis minimizes an alveolar cleft/fistula and helps reconstruct a maxillary dentoalveolar defect by approximating the native alveoli and gingivae; it also creates new alveolar bone and gingiva for rapid orthodontic tooth movement.     

Concept for development of new individual treatment devices in orthodontics using 3-dimensional numerical simulation of bone remodeling]

The present study is part of a research project that includes different components for the simulation of orthodontic tooth movement and comparing experimental results. This concept includes the development of a bone remodelling algorithm, as well as experimental studies on tooth movement. After the acquisition and evaluation of specific experimental data of the patient's situation, the individual components have to be integrated to verify and forecast tooth movement. The aim is to design individual treatment devices as well as to shorten treatment while making it more effective. The geometry of the teeth and that of the surrounding alveolar bone both influence the orthodontic tooth movement. For this reason, an exact morphological tooth model for the valid simulation of the tooth movement is needed, and can be constructed from computed tomography data. Simulation of tooth movement can then be compared with "in vivo" measurements of the orthodontic tooth movement. In this study, a specially developed hybrid retraction spring is employed. This spring enables the application of a defined, almost constant force system. The "in vivo" determined tooth movement is simulated with the aid of special positioning and measuring devices. Meanwhile, the active force system can be determined by 6-component force/moment sensors. The experimentally measured force system, "in vivo" measurements of tooth movement and the CT model are now available for numerical simulation for the first time.     

A novel adipocytokine, vaspin inhibits platelet-derived growth factor-BB-induced migration of vascular smooth muscle cells

Orthodontic treatment induces various biological responses, including tooth movement and remodeling of alveolar bone. Although some studies have investigated the contribution of orthodontic procedures to changes in saliva conditions, little is known about the effects of different treatment durations on the saliva proteome. To identify the discriminating protein profiles in unstimulated whole saliva of orthodontic patients with different treatment durations, we used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead, and peptide mass fingerprints were created by scanning MS signals. Saliva samples from 40 patients (10 in each of four groups: the group without an appliance and groups under treatment for 2, 7, and 12 months) were analyzed. The results showed eight mass peaks with significant differences. Furthermore, mass peak intensities at proteins 1817.7, 2010.7, 2744 and 2710.2 Da represented a steady time-dependent increasing trend, whereas protein 4134 Da exhibited a decreasing tendency. Differential expression of the peptidome profile also occurred in the multiple comparisons, and we established a fitting model. Thus, the potential discriminating biomarkers investigated in this study reflected the complicated changes in periodontal tissues during orthodontic treatment and indicated dynamic interactions between orthodontic treatment and the saliva proteome. The results provide novel insights into alterations in salivary proteins due to different orthodontic treatment durations and may lead to the development of a therapeutic monitoring strategy for orthodontics.     

A visco-elastic model for the prediction of orthodontic tooth movement

This study presents a biomechanical model of orthodontic tooth movement. Although such models have already been presented in the literature, most of them incorporate computationally expensive finite elements (FE) methods to determine the strain distribution in the periodontal ligament (PDL). In contrast, the biomechanical model presented in this work avoids the use of FE methods. The elastic deformation of the PDL is modelled using an analytical approach, which does not require setting up a 3D model of the tooth. The duration of the lag phase is estimated using the calculated hydrostatic stresses, and bone remodelling is predicted by modelling the alveolar bone as a viscous material. To evaluate the model, some typically used motion patterns were simulated and a sensitivity analysis was carried out on the parameters. Results show that despite some shortcomings, the model is able to describe commonly used motion patterns in orthodontic tooth movement, in both single- and multi-rooted teeth.     

Tension force-induced bone formation in orthodontic tooth movement via modulation of the GSK-3β/β-catenin signaling pathway

Orthodontic force-induced osteogenic differentiation and bone formation at tension sites play a critical role in orthodontic tooth movement. However, the molecular mechanism underlying this phenomenon is poorly understood. In the current study, we investigated the involvement of the GSK-3β/β-catenin signaling pathway, which is critical for bone formation during tooth movement. We established a rat tooth movement model to test the hypothesis that orthodontic force may stimulate bone formation at the tension site of the moved tooth and promote the rate of tooth movement via regulation of the GSK-3β/β-catenin signaling pathway. Our results showed that continued mechanical loading increased the distance between the first and second molar in rats. In addition, the loading force increased bone formation at the tension site, and also increased phospho-Ser9-GSK-3β expression and β-catenin signaling pathway activity. Downregulation of GSK-3β activity further increased bone parameters, including bone mineral density, bone volume to tissue volume and trabecular thickness, as well as ALP- and osterix-positive cells at tension sites during tooth movement. However, ICG-001, the β-catenin selective inhibitor, reversed the positive effects of GSK-3β inhibition. In addition, pharmaceutical inhibition of GSK-3β or local treatment with β-catenin inhibitor did not influence the rate of tooth movement. Based on these results, we concluded that GSK-3β/β-catenin signaling contributes to the bone remodeling induced by orthodontic forces, and can be used as a potential therapeutic target in clinical dentistry.     

Expression of genes for gelatinases and tissue inhibitors of metalloproteinases in periodontal tissues during orthodontic tooth movement

Orthodontic tooth movement progresses by a combination of periodontal ligament (PDL) tissue and alveolar bone remodeling processes. Besides the remodeling of alveolar bone around the moving teeth, the major extracellular matrix (ECM) components of PDLs, collagens, are degenerated, degraded, and restructured. Matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), act in a co-ordinated fashion to regulate the remodeling of periodontal tissues. We hypothesized that the expression levels of the genes for MMP-2, MMP-9, and TIMPs 1–3 are increased transiently in the periodontal tissue during orthodontic tooth movement. To test this hypothesis, we employed an animal model of tooth movement using rats, as well as in situ hybridization to analyze the expression levels of Mmp-2, Mmp-9, and Timps 1-3. The expression levels of these genes increased transiently in cells of periodontal tissues, which include cementoblasts, fibroblasts, osteoblasts, and osteoclasts, at the compression side of the moving teeth. The transient increases in gene expression at the tension side were mainly limited to osteoblasts and cementoblasts. In conclusion, the expression levels of Mmp-2, Mmp-9, and Timps 1-3 increase transiently during orthodontic tooth movement at both the tension and compression sides. The expression of these genes is regulated differentially in the periodontal tissue of the tension side and compression side. This altered pattern of gene expression may determine the rate and extent of remodeling of the collagenous ECM in periodontal tissues during orthodontic tooth movement.     

Biological aspects of orthodontic tooth movement: A review of literature

This review of literature describes the cellular and molecular biology of orthodontic tooth movement, including various theories and effect of chemical mediators on tooth movement. The better understanding of the tooth movement mechanism will inspire the clinicians to design and implement effective appliances that will result in maximum benefits and minimum tissue damage to the patients. This paper also emphasizes the applied aspect of different medication and hormones, during orthodontic treatment, on the signaling molecules which produce bone remodeling.     

Investigation of effective intrusion and extrusion force for maxillary canine using finite element analysis

Abstract

Orthodontic tooth movement is mainly regulated by the biomechanical responses of loaded periodontal ligament (PDL). We investigated the effective intervals of orthodontic force in pure maxillary canine intrusion and extrusion referring to PDL hydrostatic stress and logarithmic strain. Finite element analysis (FEA) models, including a maxillary canine, PDL and alveolar bone, were constructed based on computed tomography (CT) images of a patient. The material properties of alveolar bone were non-uniformly defined using HU values of CT images; PDL was assumed to be a hyperelastic–viscoelastic material. The compressive stress and tensile stress ranging from 0.47 to 12.8?kPa and 18.8 to 51.2?kPa, respectively, were identified as effective for tooth movement; a strain 0.24% was identified as the lower limit of effective strain. The stress/strain distributions within PDL were acquired in canine intrusion and extrusion using FEA; root apex was the main force-bearing area in intrusion–extrusion movements and was more prone to resorption. Owing to the distinction of PDL biomechanical responses to compression and tension, the effective interval of orthodontic force was substantially lower in canine intrusion (80–90?g) than in canine extrusion (230–260?g). A larger magnitude of force remained applicable in canine extrusion. This study revised and complemented orthodontic biomechanical behaviours of tooth movement with intrusive–extrusive force and could further help optimize orthodontic treatment.     

Alveolar bone response distal to applied orthodontic forces in ovariectomized rats

Objectives:The aim of this study was to investigate the effect of the application of orthodontic tooth forces on the alveolar bone distal to the loaded teeth, in ovariectomized female rats.Methods:Twenty-four eight-month-old Wistar rats were divided into one group ovariectomized at the age of six months and one control. An orthodontic appliance delivering a mesial traction force of 60 gr* was placed on the right maxillary 1^st molar of all animals for 14 days. Histology of the alveolar bone, of the adjacent and distal teeth to the loaded molar and the contralateral side, was performed following euthanasia.Results:In the non-ovariectomized rats, extensive resorption was noticed in the direction of the orthodontic movement in the 2^nd and 3^rd molar interdental space, whereas the respective contralateral interdental space did not show any remodeling activity. Ovariectomized rats displayed reduced osseous tissue in the interdental space of both sides. The alveolar bone in the interradicular area of the 2^nd loaded molar revealed frontal resorption, whereas, the alveolar interradicular bone of the contralateral 2^nd molar showed internal resorption.Conclusions:In conclusion, orthodontic forces applied to the dentoalveolar complex of ovariectomized rats affect bone remodeling, even in areas distal to the site of force application. This finding should be taken into account during orthodontic treatment of women during menopause.     

CTHRC1 promotes osteogenic differentiation of periodontal ligament stem cells by regulating TAZ

Collagen triple helix repeat containing 1 (CTHRC1) is associated with bone metabolism. Alveolar bone has an ability to rapidly remodel itself to adapt its biomechanical environment and function. However, whether CTHRC1 is expressed in alveolar bone tissue and the role of CTHRC1 in alveolar bone remodeling remain unclear. We used orthodontic tooth movement (OTM) rat model to study the effects of CHTRC1 in alveolar bone remodeling in vivo. We found that CTHRC1 was expressed in normal physiological condition of osteocytes, bone matrix, and periodontal ligament cells in rat. During the OTM, the expression of CTHRC1, Runx2 and TAZ were increased. We further studied the effects of CTHRC1 on osteogenic differentiation of human periodontal ligament stem cells in vitro. CTHRC1 can positively regulate the expression of TAZ and osteogenic differentiation markers like Col1, ALP, Runx2 and OCN. Overexpression of CHTRC1 increased osteogenic differentiation of PDLSCs, which could be abolished by TAZ siRNA. Our results suggest that CTHRC1 plays an important role in alveolar bone remodeling and osteogenic differentiation of PDLSCs.