Effects of orthodontic tooth movement on the Alcian blue staining patterns of rat alveolar bone: an histochemical study

There is little information available concerning the effects of orthodontic forces on glycosaminoglycans (GAG) of alveolar bone. The present study identifies changes in Alcian blue staining intensity in rat alveolar bone undergoing resorption resulting from a heavy (25g) tipping force applied to the adjacent teeth by a separating spring. One day after force application, bone from treated animals (internal control and experimental sides) demonstrated more intense staining with Alcian blue, pH 1.0 (p less than 0.005) and pH 2.5 (p less than 0.05) than external controls (untreated animals). By day 3, the intensity of Alcian blue staining of treated alveolar bone was similar to untreated. Chondroitinase AC, ABC and testicular hyaluronidase predigestion did not completely block the staining reaction, suggesting that both GAG and noncollagenous proteins were demonstrated. Mean cross-sectional areas of the interdental septum of the experimental side were nearly 44% less than that of the internal control side after 3 days and nearly 62% less after 5 days. The study suggested that alterations in bone GAG levels occurred prior to tooth movement as histochemical changes occurred after force application but before initiation of significant septal resorption. A precise appraisal of the types of macromolecules effected awaits future biochemical analysis. The results of the present work strongly suggest the use of an external control group for future studies, as Alcian blue staining reactions of the internal control side of treated animals were not similar to those of external controls.     

Contribution of membrane-associated prostaglandin E2 synthase to bone resorption

This study initially confirmed that, among prostaglandins (PGs) produced in bone, only PGE(2) has the potency to stimulate osteoclastogenesis and bone resorption in the mouse coculture system of osteoblasts and bone marrow cells. For the PGE(2) biosynthesis two isoforms of the terminal and specific enzymes, membrane-associated PGE(2) synthase (mPGES) and cytosolic PGES (cPGES) have recently been identified. In cultured mouse primary osteoblasts, both mPGES and cyclooxygenase-2 were induced by the bone resorptive cytokines interleukin-1, tumor necrosis factor-alpha, and fibroblast growth factor-2. Induction of mPGES was also seen in the mouse long bone and bone marrow in vivo by intraperitoneal injection of lipopolysaccharide. In contrast, cPGES was expressed constitutively both in vitro and in vivo without being affected by these stimuli. An antisense oligonucleotide blocking mPGES expression inhibited not only PGE(2) production, but also osteoclastogenesis and bone resorption stimulated by the cytokines, which was reversed by addition of exogenous PGE(2). We therefore conclude that mPGES, which is induced by and mediates the effects of bone resorptive stimuli, may make a target molecule for the treatment of bone resorptive disorders.     

Impaired bone resorption to prostaglandin E2 in prostaglandin E receptor EP4-knockout mice

Prostaglandin E(2) (PGE(2)) acts as a potent stimulator of bone resorption. In this study, we first clarified in normal ddy mice the involvement of protein kinase A and induction of matrix metalloproteinases (MMPs) in PGE(2)-induced bone resorption, and then identified PGE receptor subtype(s) mediating this PGE(2) action using mice lacking each subtype (EP1, EP2, EP3, and EP4) of PGE receptor. In calvarial culture obtained from normal ddy mice, both PGE(2) and dibutyryl cyclic AMP (Bt(2)cAMP) stimulated bone resorption and induced MMPs including MMP-2 and MMP-13. Addition of an inhibitor of protein kinase A, H89, or an inhibitor of MMPs, BB94, significantly suppressed bone-resorbing activity induced by PGE(2.) In calvarial culture from EP1-, EP2-, and EP3-knockout mice, PGE(2) stimulated bone resorption to an extent similar to that found in calvaria from the wild-type mice. On the other hand, a marked reduction in bone resorption to PGE(2) was found in the calvarial culture from EP4-knockout mice. The impaired bone resorption to PGE(2) was also detected in long bone cultures from EP4-knockout mice. Bt(2)cAMP greatly stimulated bone resorption similarly in both wild-type and EP4-knockout mice. Induction of MMP-2 and MMP-13 by PGE(2) was greatly impaired in calvarial culture from EP4-knockout mice, but Bt(2)cAMP stimulated MMPs induction similarly in the wild-type and EP4-knockout mice. These findings suggest that PGE(2) stimulates bone resorption by a cAMP-dependent mechanism via the EP4 receptor.     

alpha-Lipoic acid inhibits inflammatory bone resorption by suppressing prostaglandin E2 synthesis

alpha-Lipoic acid (LA) has been intensely investigated as a therapeutic agent for several pathological conditions, including diabetic polyneuropathy. In the present study, we examined the effects of LA on osteoclastic bone loss associated with inflammation. LA significantly inhibited IL-1-induced osteoclast formation in cocultures of mouse osteoblasts and bone marrow cells, but LA had only a marginal effect on osteoclastogenesis from bone marrow macrophages induced by receptor activator of NF-kappaB ligand (RANKL). LA inhibited both the sustained up-regulation of RANKL expression and the production of PGE2 induced by IL-1 in osteoblasts. In addition, treatment with either prostaglandin E2 (PGE2) or RANKL rescued IL-1-induced osteoclast formation inhibited by LA or NS398, a specific cyclooxygenase-2 (COX-2) inhibitor, in cocultures. LA blocked IL-1-induced PGE2 production even in the presence of arachidonic acid, without affecting the expression of COX-2 and membrane-bound PGE2 synthase. Dihydrolipoic acid (the reduced form of LA), but not LA, attenuated recombinant COX-2 activity in vitro. LA also inhibited osteoclast formation and bone loss induced by IL-1 and LPS in mice. Our results suggest that the reduced form of LA inhibits COX-2 activity, PGE2 production, and sustained RANKL expression, thereby inhibiting osteoclast formation and bone loss in inflammatory conditions.     

Study of bone remodeling in corticotomy-assisted orthodontic tooth movement in rats

The goal of this study was to determine the structure change of the alveolar bone and the expression of a group of bone remodeling-related factors. Sixty healthy male Wistar rats were randomly divided into three groups. Selective alveolar decortication (SAD), tooth movement (TM), and “combined therapy” (SAD+TM) was performed in group I, II, and III, respectively. On days 0, 7, 14, 21, and 42, a Micro-CT scan was performed on the maxillary alveolar bone and tooth. In addition, on days 0, 7, 14, 21, 28, and 42, some of the rats were killed by cervical dislocation and tissues were harvested. Analysis of scan data revealed a significant decrease in bone density of the alveolar bone at 14 days post-surgery, and increased at 42 days post-surgery to a level higher than that before the surgery. Microarray and bioinformatics analysis were performed to explore gene expression profile in three groups (SAD, TM, and SAD+TM), and a large number of differentially expressed genes were identified. In addition, real-time polymerase chain reaction was performed to determine the expression of bone remodeling-related factors. The expression of osteoblast-related cytokines, including osteopontin, bone sialoprotein, and osteocalcin, and osteoclast regulators macrophage-colony stimulating factor (M-CSF) and RANKL (activator of nuclear factor KB receptor ligand) were increased in group III, suggesting that there was increased bone synthesis and activation of bone absorption. Moreover, group III had a unique alveolar bone remodeling pattern: RANKL and osteoprotegerin-promoted alveolar remodeling. In conclusion, during the early stage of orthodontic tooth movement, corticotomy can accelerate the movement of teeth, modulate the state of bone metabolism, and activate osteogenesis and osteoclast, which support the theory of regional acceleratory phenomenon.     

Sympathectomy causes increased root resorption after orthodontic tooth movement in rats: immunohistochemical study

Accumulating evidence suggests that the sympathetic nervous system modulates inflammatory responses and bone remodeling. We have studied the effects of sympathectomy and orthodontic tooth movement (OTM) on root resorption, immunocompetent cell recruitment, neuropeptide, neurokinin-1 receptor (NK1-R), and interleukin 6 (IL-6) expression. Experimental rats (n=8) had the right superior cervical ganglion surgically removed, whereas control rats (n=6) underwent sham surgery. Three days later, all rats had the right maxillary first molar moved mesially by an orthodontic appliance. The rats were perfused 13 days later, and the right maxillae were processed for immunohistochemistry by using primary antibodies directed against ED1 antigen, CD43, substance P (SP), NK1-R, neuropeptide Y (NPY), and IL-6. Following OTM, sympathectomized (SCGx) rats had significantly more root resorption (P<0.01) and SP-immunoreactive (IR) fibers (P=0.01) in the compressed periodontal ligament (PDL) compared with control rats. There was a significant decrease in recruitment of CD43+ cells in the pulp after OTM in SCGx rats compared with control rats (P=0.02). An upregulation of NK1-R immunoreactivity was observed surrounding the hyalinized tissue, and an increase in the number of NK1-R IR cells and density of SP-IR fibers was present in first molar pulp of all rats. NPY-IR fibers were absent in the compressed PDL of SCGx and control rats. Thus, OTM induces remodeling not only around the periodontal tissues, but also in the dental pulp. The sympathetic nerves have an inhibitory effect on hard tissue resorption and a stimulatory effect on CD43+ cell recruitment after OTM.This study was supported by the Norwegian Research Council     

Three-dimensional analysis of orthodontic tooth movement

A three-dimensional finite element model was used to investigate the biomechanical response of an upper canine tooth. The physical model was developed from ceramic replicas and X-rays, and consisted of cancellous and cortical bone, the periodontal ligament, dentine and pulp chamber. Horizontal forces were applied at the tip of the crown and at the cervical margin and a rotational force was applied at the cervical margin of the tooth crown. The resulting displacements and stress field for each load case are presented with particular emphasis being placed on the response of the periodontal ligament. The investigation shows that quantitative information on initial tooth movement can be accurately predicted and used to evaluate the response of orthodontic treatment.     

Some properties of prostaglandin E2 receptors in rabbit alveolar bone cell membranes

[3H]prostaglandin E2 (PGE2) binding receptors exist in rabbit alveolar bone cell membranes. The presence of high (Kd = 3.9 X 10(-9) M) and low (Kd = 8.8 X 10(-8) M) affinity binding sites of [3H]PGE2 was demonstrated. The saturation values of [3H]PGE2 for high and low affinity binding sites were 0.13 pmol/mg protein and 1.22 pmol/mg protein, respectively. The digestion of the membranes with pronase, phospholipase C, D and neuraminidase led to a decrease of [3H]PGE2 binding but phospholipase A2 did not.     

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.     

Tissue changes in the rabbit periodontal ligament during orthodontic tooth movement

In this (semi) quantitative animal study the reaction of the periodontal ligament (PDL) to experimental tooth movement is described. To this end, rabbit first incisors were moved sideways with helical torsion springs for periods varying from 3-24 hours. The initial force of the springs was 50 gf. The histomorphology of the PDL was studied in 5 microns thick plastic sections. Comparison with control animals and animals wearing passive springs showed that tooth movement leads to an increased trauma in the PDL within only a few hours. This trauma is characterized by hyalinization, tears and ruptures in the fibres and blood vessels, and by the presence of extravascular erythrocytes and pyknosis. Tissue damage significantly increased with time. After 24 hours of tooth movement, the PDL fibers are compressed or stretched in 68% of the sections and the blood vessels in the PDL are compressed or stretched in 62% of the sections. Even in the controls, more than 15% of the sections displayed slightly stretched or compressed fibers, and about 10% showed slightly compressed or stretched blood vessels. This indicates that some damage is regularly present in a normally functioning PDL. Increases in the percentage of sections with blood vessel compression are found in all groups wearing passive springs, especially after 6 hours. A high concordancy in compression and tension patterns of blood vessels and fibers is present in 83% of the sections. Pyknotic cells are practically confined to areas with compressed PDL fibers in rabbits wearing active springs. Extravascular erythrocytes were found in sections with all types of fiber patterns. A significant majority of extravascular erythrocytes, however, was found in areas with compressed fibers.     

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.     

Continuously applied compressive pressure induces bone resorption by a mechanism involving prostaglandin E2 synthesis

In previous research, we devised a specific culture chamber to examine the effect of continuously applied compressive pressure (CCP) on bone formation and resorption. The chamber was infused with compressed mixed gases with different O2 and CO2 composition to maintain the pO2, pCO2, and pH in the culture medium under pressures of +0.5 atm (1.5 atm total) to +2.0 atm (3.0 atm total) at the same levels as those at the ordinary pressure (1 atm). Using the specific culture chamber, we demonstrated that CCP greatly suppressed the differentiation of mouse osteoblast-like MC3T3-E1 cells. The inhibition by CCP appeared to be mediated by prostaglandin E2 (PGE2). In the present study, we examined the effect of CCP on osteoclastic bone resorption. CCP treatment of mouse bone marrow culture markedly increased both the PGE2 production and the number of tartrate-resistant acid phosphatase (TRACP)-positive mononuclear cells (possibly precursors of multinucleated osteoclasts). An autoradiographic study using [125I]-salmon calcitonin showed clearly that those TRACP-positive cells had calcitonin receptors. The CCP effect was the greatest at +1.0 atm (2.0 atm total). Isobutylmethylxanthine potentiated the production of TRACP-positive cells induced by CCP. Adding indomethacin completely inhibited both the TRACP-positive cell formation and the PGE2 production induced by CCP. CCP also increased the release of 45Ca from prelabeled mouse calvaria during later stages (2-6 days) of the 6-day culture period. CCP markedly increased PGE2 but not interleukin 1 in the culture media of mouse calvaria. These results indicate that, besides inhibiting osteoblast differentiation, CCP stimulates bone resorption by generating new osteoclasts through a mechanism involving PGE2 production.     

Expression pattern of YAP and TAZ during orthodontic tooth movement in rats

Orthodontic tooth movement (OTM) is a periodontal tissue remodeling and regeneration process that is caused by bio-mechanical stimulation. This mechanical–chemical transduction process involves a variety of biological factors and signaling pathways. It has been shown that the Hippo-YAP/TAZ signaling pathway plays a pivotal role in the mechanical–chemical signal transduction process. Moreover, YAP and TAZ proteins interact with RUNX family proteins via different mechanisms. To explore the regulation of the Hippo signaling pathway during periodontal tissue remodeling, we examined the upper first molar OTM model in rats. We examined YAP, TAZ and RUNX2 expression at 12 hours, 24 hours, 2 days (2d), 4 days, 7 days (7d) and 14 days (14d) after force application. Haemotoxylin and eosin staining, immunohistochemical staining and western blot analysis were used to examine the expression level and localization of these proteins. We found that YAP, TAZ and RUNX2 expression started increasing at 2d, YAP and TAZ expression was proportional to the orthodontic force applied until peaking at 7d, and at 14d the expression started to decrease. YAP and TAZ were observed in osteocytes, bone matrix and periodontal ligament cells during OTM. Furthermore, using double labeling immunofluorescence staining, we found that the increase in TAZ expression was associated with RUNX2 expression, however, YAP and RUNX2 showed different expression patterns. These results suggest that the Hippo-YAP/TAZ signaling pathway participates in periodontal tissue remodeling through various mechanisms; TAZ may adjust bone tissue remodeling through RUNX2 during OTM, while YAP may regulate periodontal cell proliferation and differentiation.     

Ultrastructure of alveolar bone during tooth eruption in the dog

Previous work from our laboratories has established that eruption of the permanent mandibular premolars in dogs is dependent upon the presence of the dental follicle and that it involves resorption of alveolar bone and the roots of the deciduous predecessor above and formation of alveolar bone below the developing crown. This study illustrates the topography of the bone surfaces of the crypt by scanning electron microscopy and the ultrastructure of the cells on alveolar bone surfaces during tooth eruption. Above the developing crown where the eruption pathway forms, the bone surface is a pitted sheet, the characteristic topographic feature of bone resorption; between the crown and the mandibular canal, the bone surface has numerous interconnecting trabeculae. Transmission electron microscopy of bone cells lining the eruption pathway area of the crypt showed numerous osteoclasts with adjacent mononuclear cells. Both cell types contained specific, membrane-bound cytoplasmic vesicles shown by the work of others to be characteristic features of osteoclasts and their precursors. Basal trabeculated bone in the crypt was covered by plump osteoblasts. These data show that the metabolic events in alveolar bone associated with tooth eruption have the appropriate cellular and bony surface correlates and that the suspected control of alveolar bone resorption by the dental follicle may be mediated by its recruiting and directing to adjacent bone surfaces the mononuclear precursors of osteoclasts.     

Effects of prostaglandin E2 on the subcellular localization of Epac-1 and Rap1 proteins during Fcgamma-receptor-mediated phagocytosis in alveolar macrophages

Recent studies have demonstrated a central role for the exchange protein activated by cAMP (Epac) in the inhibition of Fcgamma-receptor-mediated phagocytosis and bacterial killing by prostaglandin E(2) (PGE(2)) in macrophages. However, the subcellular localization of Epac, and its primary target Rap1, has yet to be determined in primary macrophages. Therefore, we used immunofluorescent techniques and phagosome isolation to localize Epac-1 and Rap1 in alveolar macrophages. Epac-1 was predominantly expressed on punctate and tubular membranes throughout the cell body; on the plasma membrane; and co-localized with microtubule organizing centers (MTOCs). Rap1 was abundant on punctate membranes, less abundant on plasma membrane, and also found on MTOCs. Following PGE(2) treatment, Epac-1, but not Rap1, accumulated on the nuclear envelope and disappeared from MTOCs. By immunofluorescent microscopy, both Epac-1 and Rap1 were seen to associate with phagosomes containing IgG-opsonized beads, but this association appeared weak, as we failed to observe such interactions in phagosomes isolated from cells at various time points after bead ingestion. Strikingly, however, Epac-1, but not Rap1, appeared to accumulate on maturing phagosomes, but only after PGE(2) treatment (or treatment with a selective Epac-1 agonist). This association was confirmed in isolated phagosome preparations. The changes in Epac-1 localization were too slow to account for the inhibitory effects of PGE(2) on phagocytosis. However, the appearance of Epac-1 on late phagosomes following PGE(2) treatment might be important for suppressing H(2)O(2) production and inhibiting the killing of intraphagosomal pathogens. The absence of Rap1 on late phagosomes suggests that the effect of Epac-1 might not require Rap1.     

Stimulation of prostaglandin E2 and bone resorption by recombinant human interleukin 1 alpha in fetal mouse bones

Recombinant human interleukin 1 alpha (rhIL-1 alpha) stimulates prostaglandin E2 and bone resorption in cultured forearm bones of fetal mouse in a dose-dependent manner: the minimal rhIL-1 alpha to elicit a significant bone resorption was 1.6 ng/ml (89 pM). The half maximal concentrations to elicit bone resorption and thymocyte proliferation were 3.3 ng/ml (183 pM) and 0.31 ng/ml (17 pM), respectively. The bone resorbing activity induced by IL-1 was partially inhibited by indomethacin and hydrocortisone, and completely inhibited by anti-IL 1-antibody. There was a good correlation between PGE2 production and bone resorption induced by IL-1 alpha. These results suggest that rhIL-1 alpha stimulates bone resorption at approximately 10 times the concentrations necessary for thymocyte proliferation and that PGE2 produced in the bone is at least in part involved in osteoclastic bone resorption.     

Stimulation of bone formation by prostaglandin E2

We examined the effect of prostaglandin E2 (PGE2), in the presence or absence of cortisol, on bone formation in 21-day fetal rat calvaria maintained in organ culture for 24 to 96 h. [3H]Thymidine and [3H] proline incorporation were used to assess DNA and collagen synthesis, respectively. Changes in dry weight and DNA content were assessed after 96 h. PGE2 (10(-7) M) stimulated both DNA and collagen synthesis in calvaria. The effect on DNA synthesis was early (24 h), transient and limited to the periosteum. Collagen synthesis was stimulated at a later time (96 h), predominantly in the central bone. Cortisol (10(-7) M) inhibited DNA and collagen synthesis. The addition of PGE2 reversed the inhibitory effects of cortisol on DNA synthesis and content and increased collagen synthesis in central bone to levels above control untreated cultures. We conclude that PGE2 has stimulatory effects on bone formation and can reverse the inhibitory effects of cortisol. Hence the effects of cortisol may be mediated in part by their ability to reduce the endogenous production of prostaglandins.     

Apoptotic bone cells may be engulfed by osteoclasts during alveolar bone resorption in young rats

The alveolar bone is a suitable in vivo physiological model for the study of apoptosis and interactions of bone cells because it undergoes continuous, rapid and intense resorption/remodelling, during a long period of time, to accommodate the growing tooth germs. The intensity of alveolar bone resorption greatly enhances the chances of observing images of the extremely rapid events of apoptosis of bone cells and also of images of interactions between osteoclasts and osteocytes/osteoblasts/bone lining cells. To find such images, we have therefore examined the alveolar bone of young rats using light microscopy, the TUNEL method for apoptosis, and electron microscopy. Fragments of alveolar bone from young rats were fixed in Bouin and formaldehyde for morphology and for the TUNEL method. Glutaraldehyde-formaldehyde fixed specimens were processed for transmission electron microscopy. Results showed TUNEL positive round/ovoid structures on the bone surface and inside osteocytic lacunae. These structures--also stained by hematoxylin--were therefore interpreted, respectively, as osteoblasts/lining cells and osteocytes undergoing apoptosis. Osteoclasts also exhibited TUNEL positive apoptotic bodies inside large vacuoles; the nuclei of osteoclasts, however, were always TUNEL negative. Ultrathin sections revealed typical apoptotic images--round/ ovoid bodies with dense crescent-like chromatin--on the bone surface, corresponding therefore to apoptotic osteoblasts/lining cells. Osteocytes also showed images compatible with apoptosis. Large osteoclast vacuoles often contained fragmented cellular material. Our results provide further support for the idea that osteoclasts internalize dying bone cells; we were however, unable to find images of osteoclasts in apoptosis.     

Periodontal ligament cell kinetics following orthodontic tooth movement.

The population of periodontal ligament (PDL) fibroblasts examined in this study may include osteogenic progenitor cells. PDL fibroblast and osteoblast kinetics in the periodontal ligament of the rat were measured following orthodontic stimulation of bone formation. Both single and multiple injections of tritiated thymidine (3H-TdR) were used. In single injection experiments, the peak percentage of PDL fibroblasts labeled with 3H-TdR is 15% at 22 hr post-stimulation. In multiple injection experiments, the total percentage of fibroblasts in the PDL which respond by synthesizing DNA is 50%. 3H-TdR-labeled osteoblasts appear at the same rate as, but with a time delay after, the labeled fibroblasts. Following stimulation, the most likely source of osteoblasts at the bbone forming site is not only fibroblasts which make DNA, divide, then differentiate, but also fibroblasts which either are differentiated to osteoblasts without DNA synthesis and cell division, or are released from G2 block by the orthodontic stimulation.     

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.