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.     

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.     

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.     

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.     

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。     

HSPA1A is upregulated in periodontal ligament at early stage of tooth movement in rats

Heat shock proteins (HSPs) are molecular chaperones that maintain intracellular protein homeostasis and ensure survival of cells. Continuous orthodontic force on the tooth is considered to be a type of physical stress loaded to the periodontal ligament (PDL). However, little is known about the role of HSPs during tooth movement. This study was performed to examine the expression of HSPs in the PDL during tooth movement using laser microdissection, microarray analysis, real-time RT-PCR and immunohistochemistry. Gene expression of HSPA1A in the pressure zone of the PDL was higher during 6 h of tooth movement than in the control group. Expression of HSPA1A decreased with time. HSPA1A was also detected in the pressure zone of the PDL at the protein level 24 h after the initial tissue change. These results strongly suggest that expression of HSPA1A in the PDL during early stages of tooth movement is a critical factor for tissue reaction.     

Numerical study of tension and strain distribution around rat molars]

A knowledge of the mechanical processes triggered in the bone and periodontal ligament (PDL) by orthodontic forces applied to a tooth is of decisive importance for an understanding of the subsequent remodelling around the tooth. To investigate these mechanical relationships, three-dimensional finite element (FE) models of the first lower molar in the rat were established. On the basis of digitized serial histological sections, these FE models were generated semi-automatically. Using various simplified geometrical variations, an appropriate FE model for the analysis of the stress and strain distributions was established. The numerical analyses were carried out under a mesially directed force of 0.1 N. Stress distributions in the bone and PDL showed a similar pattern, while strains in the bone were lower than in the PDL by a factor of 10-5. The data confirm the assumption that strain patterns in the PDL may be the key stimulus of bone remodelling.     

Differential expression of osteoblast and osteoclast chemmoatractants in compression and tension sides during orthodontic movement

Orthodontic tooth movement is achieved by the remodeling of alveolar bone in response to mechanical loading, and is supposed to be mediated by several host mediators, such as chemokines. In this study we investigated the pattern of mRNAs expression encoding for osteoblast and osteoclast related chemokines, and further correlated them with the profile of bone remodeling markers in palatal and buccal sides of tooth under orthodontic force, where tensile (T) and compressive (C) forces, respectively, predominate. Real-time PCR was performed with periodontal ligament mRNA from samples of T and C sides of human teeth submitted to rapid maxillary expansion, while periodontal ligament of normal teeth were used as controls. Results showed that both T and C sides exhibited significant higher expression of all targets when compared to controls. Comparing C and T sides, C side exhibited higher expression of MCP-1/CCL2, MIP-1α/CCL3 and RANKL, while T side presented higher expression of OCN. The expression of RANTES/CCL5 and SDF-1/CXCL12 was similar in C and T sides. Our data demonstrate a differential expression of chemokines in compressed and stretched PDL during orthodontic tooth movement, suggesting that chemokines pattern may contribute to the differential bone remodeling in response to orthodontic force through the establishment of distinct microenvironments in compression and tension sides.     

Focal adhesion kinase mediates β-catenin signaling in periodontal ligament cells

Periodontal ligament (PDL) cells convert the orthodontic forces into biological responses by secreting signaling molecules to induce modeling of alveolar bone and tooth movement. Beta-catenin pathway is activated in response to mechanical loading in PDL cells. The upstream signaling pathways activated by mechanical loading resulting in the activation of β-catenin pathway through Wnt-independent mechanism remains to be characterized. We hypothesized that mechanical loading induces activation of β-catenin signaling by mechanisms that dependent on focal adhesion kinase (FAK) and nitric oxide (NO). We found that mechanical or pharmacological activation of β-catenin signaling in PDL cells upregulated the expression of β-catenin target genes. Pre-treatment of PDL cells with FAK inhibitor-14 prior to mechanical loading abolished the mechanical loading-induced phosphorylation of Akt and dephosphorylation of β-catenin. PDL cells pre-treated with NO donor or NO inhibitor and subjected to mechanical loading. Western blot analysis showed that the mechanical loading or pre-treatment with NO donor increased the levels of dephosphorylated β-catenin, pAkt, and pGSK-3β. Pre-treatment with NO inhibitor blocked the mechanical loading-induced phosphorylation of Akt and dephosphorylation of β-catenin. These data indicate that mechanical loading-induced β-catenin stabilization in PDL cells involves phosphorylation of Akt by two parallel pathways requiring FAK and NO.     

A device for the application of known simulated orthodontic forces to human cells in vitro

Connective tissues are responsive to mechanical forces. In orthodontic tooth movement it appears that the periodontal ligament (PDL) is the source of a pleuropotential cell population and extracellular matrix structure which translates mechanical perturbation information into a host of cellular events. These include proliferation, repair, differentiation, and shape change. We have designed, built, and tested a simple, adaptable machine which enables us to examine molecular changes or events in the cell nucleus, cell membrane, and the cytoskeleton of any eukasytic cell that will adhere to a membrane. These responses to clinically simulated forces applied to an in vitro system can be measured.     

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.     

Mechanical stress alters protein O‐GlcNAc in human periodontal ligament cells

Protein O‐linked N‐acetylglucosamine (O‐GlcNAc) is a post‐translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors. However, O‐GlcNAc's response to mechanical stress has not been investigated yet. As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O‐GlcNAc in PDL cells. In this study, PDL cells isolated from premolars extracted for orthodontic indications were exposed to 0, 1.5, 3, 7 and 14 g/cm² compression forces for 12 hours. Cell viability was measured by flow cytometry, and protein O‐GlcNAc was analysed by Western blot. Cellular structure and intracellular distribution of O‐GlcNAc was studied by immunofluorescence microscopy. We found that between 1.5 and 3 g/cm² mechanical compression, O‐GlcNAc significantly elevated; however, at higher forces O‐GlcNAc level was not increased. We also found that intracellular localization of O‐GlcNAc proteins became more centralized under 2 g/cm² compression force. Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O‐GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.     

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.     

The divergent expression of periostin mRNA in the periodontal ligament during experimental tooth movement

A novel 90-kDa protein named periostin, which is preferentially expressed in the periosteum and the periodontal ligament (PDL), may play a role in bone metabolism and remodeling. However, the precise role of periostin in the PDL remains unclear. Therefore, we examined the expression of periostin mRNA during experimental tooth movement. Experimental tooth movement was achieved in 7-week-old male Sprague-Dawley rats. In control specimens without tooth movement, the expression of periostin mRNA was uniformly observed in the PDL surrounding the mesial and distal roots of the upper molars and was weak in the PDL of the root furcation area. The periostin mRNA-expressing cells were mainly fibroblastic cells in the PDL and osteoblastic cells on the alveolar bone surfaces. The divergent expression of periostin mRNA in the PDL began to be observed at 3 h and continued up to 96 h after tooth movement. The maximum changes, which showed stronger staining in the pressure sites than in the tension sites, were observed at 24 h. The expression of periostin mRNA in the PDL 168 h after tooth movement exhibited a similar distribution to that of the control specimens. These results suggest that periostin is one of the local contributing factors in bone and periodontal tissue remodeling following mechanical stress during experimental tooth movement.     

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.     

Simulation of bone remodelling in orthodontic treatment

Orthodontic treatments not only displace irregular teeth but also induce responses in surrounding bone tissues. Bone remodelling is regarded as the regulatory mechanism triggered by mechanical loading. This study was aimed at investigating the effect of orthodontic loading on both tooth movement and neighbouring bone density distribution. A set of computational algorithms incorporating both external and internal remodelling mechanisms was implemented into a patient-specific 3D finite element (FE) model to investigate and analyse orthodontic treatment under four typical modes of orthodontic loading. The consequence of orthodontic treatment was reproduced numerically by using this FE-based technique. The results indicated that the diverse modes of orthodontic loading would result in different magnitudes of tooth movement and particular morphology of bone density distribution. It is illuminated that the newly developed algorithms may replicate the clinical situation more closely compared with the previous proposed method.     

Mechanical responses of the periodontal ligament based on an exponential hyperelastic model: a combined experimental and finite element method

The V–W exponential hyperelastic model is adopted to describe the instantaneous elastic response of the periodontal ligament (PDL). The general theoretical framework of constitutive modeling is described based on nonlinear continuum mechanics, and the elasticity tensor used to develop UMAT subroutine is formulated. Nanoindentation experiment is performed to characterize mechanical properties of an adult pig PDL specimen. Then the experiment is simulated by using the finite element (FE) analysis. Meanwhile, the optimized material parameters are identified by the inverse FE method. The good agreement between the simulated results and experimental data demonstrates that the V–W model is capable of describing the mechanical behavior of the PDL. Therefore, the model and its implementation into FE code are validated. By using the model, we simulate the tooth movement under orthodontic loading to predict the mechanical responses of the PDL. The results show that local concentrations of stress and strain in the PDL are found.     

Time-related PDL: viscoelastic response during initial orthodontic tooth movement of a tooth with functioning interproximal contact-a mathematical model

Most anteroposterior orthodontic movements of posterior teeth have to overcome the "resistance" of adjacent teeth with functioning interproximal contacts. The aim of this study was to develop a mathematical model describing initial posterior tooth movement associated with functioning interproximal contacts in relation to the viscoelastic mechanical behavior of the human periodontal ligament (PDL). A linear viscoelastic 2D mathematical model was modified to depict tipping movement around the center of rotation (C(rot)) of a premolar where tipping is restrained by adjacent teeth. Equilibrium equations were applied taking into account the sagittal moment developed around the C(rot). The constants of the model were analyzed and applied to a numerical model that can simulate short-term tooth creep movement caused by a tipping force. Changes in force magnitude (0.5-3N) and crown length (6-10mm) were analyzed until no movement was observed (steady state). Premolar displacement in contact with adjacent teeth showed a non-linear progression over time with an initial sharp tipping movement followed by a transient period of 2.6-7.1min. As tipping force increased the transient period increased. A similar but smaller effect was observed with an increase in crown length. The premolar initial displacement within the arch (3.2-19.5microm) is about seven-fold smaller than retraction/protraction movement of an incisor. These suggest reduction in tooth displacement when functioning interproximal contact is present and clinically recommend establishing a space in the direction of tooth displacement before tooth movement.