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.     

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.     

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.     

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.     

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.     

Effects of Equiaxial Strain on the Differentiation of Dental Pulp Stem Cells without Using Biochemical Reagents

During orthodontic treatments, applied mechanical forces create strain and result in tooth movement through the alveolar bone. This response to mechanical strain is a fundamental biological reaction. The present study evaluated the effect of equiaxial strain within the range of orthodontic forces on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). Following isolation and culture of hDPSCs, 3rd passage cells were transferred on a silicone membrane covered with collagen. Cell adhesion to the membrane was evaluated under scanning electron microscope (SEM). Cells were divided into three groups: the first group was placed in a conventional culture medium, transferred to an equiaxial stretching device (3% strain for 2 weeks). The positive control was placed in an osteogenic medium with no mechanical strain. The negative control group was placed in the conventional culture medium with no mechanical strain either. Study groups were evaluated for expression of osteogenic markers (Alkaline phosphatase and Osteopontin) with immunofluorescence and real time PCR. SEM images revealed optimal adhesion of cells to the silicone membrane. Immunofluorescence study demonstrated that osteocalcin expression occurred after 2 weeks in the two groups under mechanical and chemical signals. After application of equiaxial strain, level of expression of osteogenic markers was significantly higher than in the negative and positive control groups. Based on the study results, static equiaxial strain which mimics the types of orthodontic forces can result in differentiation of hDPSCs to osteoblasts. The results obtained may be used in cell therapy and tissue engineering.     

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.     

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.     

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.     

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.     

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.     

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.     

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。     

Role of Mechanical Stress-induced Glutamate Signaling-associated Molecules in Cytodifferentiation of Periodontal Ligament Cells

In this study, we analyzed the effects of tensile mechanical stress on the gene expression profile of in vitro-maintained human periodontal ligament (PDL) cells. A DNA chip analysis identified 17 up-regulated genes in human PDL cells under the mechanical stress, including HOMER1 (homer homolog 1) and GRIN3A (glutamate receptor ionotropic N-methyl-d-aspartate 3A), which are related to glutamate signaling. RT-PCR and real-time PCR analyses revealed that human PDL cells constitutively expressed glutamate signaling-associated genes and that mechanical stress increased the expression of these mRNAs, leading to release of glutamate from human PDL cells and intracellular glutamate signal transduction. Interestingly, exogenous glutamate increased the mRNAs of cytodifferentiation and mineralization-related genes as well as the ALP (alkaline phosphatase) activities during the cytodifferentiation of the PDL cells. On the other hand, the glutamate signaling inhibitors riluzole and (+)-MK801 maleate suppressed the alkaline phosphatase activities and mineralized nodule formation during the cytodifferentiation and mineralization. Riluzole inhibited the mechanical stress-induced glutamate signaling-associated gene expressions in human PDL cells. Moreover, in situ hybridization analyses showed up-regulation of glutamate signaling-associated gene expressions at tension sites in the PDL under orthodontic tooth movement in a mouse model. The present data demonstrate that the glutamate signaling induced by mechanical stress positively regulates the cytodifferentiation and mineralization of PDL cells.     

The effects of the periodontal ligament on mandibular stiffness: a study combining finite element analysis and geometric morphometrics

It is generally accepted that the periodontal ligament (PDL) plays a crucial role in transferring occlusal forces from the teeth to the alveolar bone. Studies using finite element analysis (FEA) have helped to better understand this role and show that the stresses and strains in the alveolar bone are influenced by whether and how PDL is included in FE models. However, when the overall distribution of stresses and strains in crania and mandibles are of interest, PDL is often not included in FE models, although little is known about how this affects the results. Here we study the effect of representing PDL as a layer of solid material with isotropic homogeneous properties in an FE model of a human mandible using a novel application of geometric morphometrics. The results show that the modelling of the PDL affects the deformation and thus strain magnitudes not only of the alveolar bone around the biting tooth, but that the whole mandible deforms differently under load. As a result, the strain in the mandibular corpus is significantly increased when PDL is included, while the strain in the bone beneath the biting tooth is reduced. These results indicate the importance of the PDL in FE studies. Thus we recommend that the PDL should be included in FE models of the masticatory apparatus, with tests to assess the sensitivity of the results to changes in the Young's modulus of the PDL material.     

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.     

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.     

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.     

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.     

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.