Orthodontic tooth movement in cholestatic and cirrhotic rats

OBJECTIVE: To investigate whether cirrhosis and cholestasis could influence orthodontic tooth movement. DESIGN: Basic science, animal experimental study. SETTING: This study was conducted in the Department of Pharmacology, School of Medicine at Tehran University of Medical Sciences in 2007. PARTICIPANTS: A total of 40 male Sprague-Dawley rats (150-200 g) were divided into five experimental groups: non-operated, cholestatic-sham, cirrhotic-sham, cholestatic and cirrhotic groups. METHODS: An orthodontic appliance, consisting of a 5 mm nickel titanium closed coil spring, was ligated between the maxillary right incisor and first molar of each rat to deliver an initial force of 60 g. The cholestatic and cirrhotic groups underwent a bile duct ligation operation and received an orthodontic appliance for 7 days (cholestatic group) and 28 days (cirrhotic group) after surgery. Two other groups underwent a sham operation and had an orthodontic appliance inserted after 7 (cholestatic-sham) and 28 days (cirrhotic-sham). A fifth control group underwent neither bile duct ligation operation nor sham operation. RESULTS: The cirrhotic group showed significantly increased orthodontic tooth movement (OTM), compared to all other study groups (P<0.001). The mean OTM in the cholestatic group was significantly higher than in the other three groups (two sham groups and unoperated one) (P<0.01). Bone density was also significantly decreased in the bile duct ligated (cirrhotic and cholestatic) groups (P<0.01). CONCLUSION: Our data demonstrated that biliary cirrhosis could cause a significant increase in the OTM and decrease in the bone density in rats, though there was no significant alteration in bone resorption or osteoclasts detected in such animals.     

组织工程修复区早期牙移动压力侧牙周组织的改建

目的: 探讨牙槽骨组织工程修复区内早期牙移动时压力侧的牙周改建情况,为组织工程技术在正畸中应用的安全性和可行性提供实验依据。方法: 选取30只新西兰大白兔,通过拔除下颌第一磨牙并扩大拔牙窝,建立双侧牙槽骨的超临界骨缺损,分别以实验组骨髓间充质干细胞（bone marrow mesenchymal stem cells,BMSCs）与颗粒型多孔β磷酸三钙（beta-tricalcium phosphate,β-TCP）支架复合构成的组织工程骨和对照组单纯β-TCP支架进行右侧和左侧骨缺损修复。术后8周,选取6只兔进行植骨区取材,评价2组的成骨效果。对剩余兔进行下颌两侧第二磨牙加力,近中向牵引4周。分别在加力后的第1、2、3、4周各处死6只动物,测量牙移动距离并制作组织学切片,通过H-E染色观察牙周组织变化,抗酒石酸酸性磷酸酶染色法计数压力侧破骨细胞数目。采用SPSS 19.0软件包对数据进行统计学分析。结果: 植骨术后8周,实验组成骨效果优于对照组。牵引4周后,正畸牙在实验组牙槽骨修复区内的移动量大于对照组。牵引第2、3、4周时,实验组移动牙压力侧的破骨细胞数量均高于对照组,差异具有统计学意义。结论: BMSCs复合β-TCP支架能够良好地修复牙槽骨缺损,邻牙在组织工程修复区内早期移动时,再生的牙周组织改建活跃,有加速牙移动的趋势。     

The effect of alveolar decortication on orthodontically induced root resorption

ObjectiveTo determine the effect of alveolar decortication on orthodontically induced root resorption.Materials and MethodsA total of 24 male Wistar rats (14 week old) were used. The rats were randomly divided into one of the following three groups: group 1 (control group), orthodontic tooth movement (OTM) for 2 weeks; group 2, OTM for 2 weeks + two alveolar decortications (2AD); group 3, OTM for 2 weeks + four alveolar decortications (4AD). The first molar was moved mesially for 2 weeks. Micro computed tomography was used to analyze root volume. In addition, histological sections were stained with Tartrate Resistant Acid Phosphatase (TRAP) to quantify the osteoclast number.ResultsThe buccal root volume in OTM + 4AD group was decreased by 8.92% and 6.11% when compared with the OTM-only group and OTM + 2AD group, respectively. Similarly, the other four root volumes in the OTM + 4AD group was decreased by 8.99% and 5.24% when compared with the OTM-only group and OTM + 2AD group, respectively. There was a decrease in buccal root density in the OTM + 4AD group by 4.66% and 3.56% when compared with the OTM-only group and the OTM + 2AD group, respectively. In addition, there was an increase in the number of osteoclasts by 195.73% and 98.74% in OTM + 4AD group in comparison with the OTM and OTM + 2AD group.ConclusionsThe amount of orthodontically induced root resorption was positively correlated with the extent of surgical injury used to accelerate orthodontic tooth movement.     

大鼠正畸压力侧牙周膜神经纤维超微结构变化的研究

目的：观察正畸力作用下压力侧牙周膜神经纤维超微结构的改变。方法：利用透射电镜观察15只大鼠正畸牙齿移支2d、1周、2周和3周后，压力侧牙周膜神经纤维超微结构的改变。结果：牙齿移动2d后可见粗有髓神经纤维变性，3周后尚未完全恢复。细无髓神经纤维在2d时数量稍增多，1周时达到高,逐渐减少，至3周时数恢复 正常，部分神经纤维轻度变性；细有髓神经纤维数量无明显变化，其中部分神经纤维轻度变化性。结论：在正畸力作用下，牙周膜神经纤维均发生不同程度的变化，Aβ纤维严重变性，而Aδ纤维及C纤维轻度变性，C纤维主要表现为增生。     

Effects of vitamin D deficiency on the rate of orthodontic tooth movement: An animal study

Bone remodeling and orthodontic tooth movement (OTM) are controlled by certain essential molecules, one of which is vitamin D. Increased levels of vitamin D have been associated with increased rates of OTM. The purpose of this study was to determine the effect of vitamin D deficiency on the rate of OTM, and to determine their association after applying orthodontic forces.Materials and MethodsWistar rats were divided into two groups: control group with average vitamin D levels and experimental group with induced vitamin D deficiency. Orthodontic appliances were fixed to initiate tooth movement. Distance between the reference teeth were measured in millimeters on day zero, and repeated every 7 days, till day 21.ResultsA significant difference within the experimental group was found; as well as within the control group, there was also no significant interaction between time and the type of group.ConclusionThe rate of Orthodontic tooth movement was not affected by induced vitamin D deficiency in rats.     

The role of opioid systems on orthodontic tooth movement in cholestatic rats

Endogenous opioids have been reported to accumulate in the plasma of cholestatic subjects. Another report showed that human osteoblast-like cells, MG-63, express 3 types of opioid receptors. In our laboratory we noticed that orthodontic tooth movement (OTM) is enhanced in cholestatic rats. Therefore, we suggest a possible role of opioid systems in bone remodeling and raising the rate of OTM in cholestatic conditions. To investigate this hypothesis, rat models were established and divided into 5 study groups. An orthodontic appliance, consisting of a 5 mm nickel-titanium closed coil spring, was ligated between the maxillary right incisor and first molar of each rat to deliver an initial force of 60 g. The bile duct ligated (BDL) group underwent a bile duct ligation operation and received orthodontic appliance 7 days after surgery. Another group underwent a sham operation and orthodontic appliances were inserted just as in the BDL group protocol. Surgery was performed the BDL + naltrexone group and orthodontic appliances were inserted 7 days after surgery. This group received daily subcutaneous injections of naltrexone HCI (an opioid antagonist) at 20 mg/kg at 24-hour intervals from the day of force application until the end of the study period. Another group, the naltrexone group, received naltrexone injections like the BDL + naltrexone group. A fifth control group neither underwent surgery nor received injections. Orthodontic tooth movement was measured 14 days after appliance insertion. The bile duct ligated group showed significantly increased OTM compared to all other study groups (P < .001). The difference between the OTM in the BDL + naltrexone and control groups was insignificant. This study suggests a role for opioid systems in OTM in cholestasis conditions.     

Influence of ibuprofen combined with corticotomy on tooth movement and alveolar bone remodeling in rats

ObjectivesTo investigate the effects of corticotomy-assisted orthodontic tooth movement and administration of ibuprofen on tooth movement rate and alveolar bone response.Materials and MethodsA total of 78 adult male Wistar rats were randomly assigned to five groups: one baseline group (no treatment) and four experimental groups including orthodontic tooth movement only (OTM), orthodontic tooth movement with ibuprofen (OTMI), corticotomy-assisted orthodontic tooth movement (COTM), and corticotomy-assisted orthodontic tooth movement with ibuprofen (COTMI). Corticotomy was performed on a maxillary molar unilaterally. Nickel-titanium closed-coil springs generated a 10-gram force for maxillary first molar movement. The experimental drug groups received 15 mg/kg of ibuprofen, and the other groups received reverse osmosis water. Tooth movement and bone volume fraction were evaluated by micro–computed tomography on days 0, 7, 14, and 21.ResultsThe corticotomy groups had statistically significantly higher tooth movement and lower bone volume fraction than the orthodontic groups (P < .05). The amount and rate of tooth movement were statistically significantly different between the OTM and OTMI groups, but not statistically significantly different in bone volume fraction. However, statistically significant differences were not observed in any measurements between the COTM and COTMI groups.ConclusionsIbuprofen during orthodontic tooth movement inhibited tooth movement and alveolar bone remodeling but had no effect on corticotomy-assisted orthodontic treatment.     

Effects of calcitonin on orthodontic tooth movement and associated root resorption in rats

Objectives: Our main aim was to evaluate the effects of calcitonin (CT) on orthodontic tooth movement (OTM) and orthodontic root resorption in a rat model.

Material and methods: Eighty male Wistar rats were randomly divided into five groups. Rats in the negative control group were not given any appliances or injections. All the remaining rats were used to establish a model of OTM. The positive control group were then injected with normal saline, while rats in the three experimental groups were injected with 0.2?IU, 1?IU or 5?IU/kg/day CT. Nickel-titanium closed-coil springs were used to deliver an initial 50?g mesial force to the left maxillary first molar for 14 days in rats in the positive control group and the experimental groups. Each group was randomly subdivided into two groups, one for analysis of tooth movement, tissue changes and tartrate-resistant acid phosphatase (TRAP)-positive cells in alveolar bone, the other to examine root resorption by scanning electron microscopy.

Results: The OTM distance, the number of force-induced osteoclasts and root resorption areas were significantly decreased in CT-injected rats in a dose-dependent manner.

Conclusions: Administration of CT reduces the root resorption area and may therefore be effective as a novel adjunctive orthodontic approach to diminish undesired tooth movement via enhancing anchorage or preventing relapse after OTM.     

TRAF6/c-fos在PTH加速兔下颌骨截骨术后正畸牙移动机制的初步研究

目的　研究外源性甲状旁腺激素（PTH）对下颌升支截骨术后正畸牙移动过程中肿瘤坏死因子受体相关因子6（TRAF6）和c-fos mRNA表达变化,探讨PTH加速截骨术后正畸牙移动的调控机制。方法：48只兔建立下颌升支截骨和下颌第一磨牙正畸移动模型,随机分成实验组和对照组。实验组术后间断性注射PTH 40 μg/kg,对照组皮下注射生理盐水,术后测量下颌第一磨牙近中移动速度。HE染色观察正畸牙压力侧组织形态学变化;TRAP染色计数压力侧牙周组织破骨细胞的数目;Real-time PCR检测下颌第一磨牙牙周组织中TRAF6和c-fos mRNA表达变化。结果：实验组下颌第一磨牙近中移动速度快于对照组,且实验组正畸牙压力侧破骨细胞数目较对照组多。实验组正畸牙压力侧牙周组织TRAF6和c-fos mRNA表达均高于对照组（P<0.05）。结论：外源性PTH可通过促进正畸牙压力侧牙周组织中TRAF6和c-fos mRNA表达,促进破骨细胞的成熟和分化,从而加速下颌升支截骨术后正畸牙的移动。     

Pulpal outcomes in orthodontic tooth movement in diabetes mellitus

Odontology - Diabetes mellitus impairs angiogenesis and tissue reorganization during orthodontic tooth movement (OTM). Thus, this study evaluated pulpal outcomes in orthodontic tooth movement...     

Effect of flapless osteoperforation-assisted tooth movement on atrophic alveolar ridge: Histomorphometric and gene-enrichment analysis

Objective:To investigate the effect of flapless osteoperforation on the tissue response of the atrophic alveolar ridge affected by orthodontic tooth movement (OTM).Materials and Methods:An atrophic alveolar ridge model was established in the mandibular quadrants of eight beagle dogs. As a split-mouth design, the quadrants were randomly divided into group C (OTM only) and group OP (OTM with flapless osteoperforation). The rate of OTM for 10 weeks was compared between groups, and micro-CT-based histomorphometric analysis and RNA-sequencing-based gene-enrichment analysis were performed targeting the atrophic ridge.Results:Group OP displayed more rapid tooth movement with lower bone mineral density and higher trabecular fraction in the atrophic ridge than did group C, showing no intergroup difference of total ridge volume. As contributing biological functional pathways in group OP, the genes related to osteoclast differentiation and TNF signaling pathway were up-regulated and those associated with Wnt signaling pathway and AMPK signaling pathway were down-regulated.Conclusions:Flapless osteoperforation facilitated the rate of OTM toward the atrophic ridge, maintaining low bone density, whereas it did not increase the volume of the atrophic ridge.     

Effects of bone regeneration materials and tooth movement timing on canine experimental orthodontic treatment

Objectives:To evaluate the effects of bone regeneration materials and orthodontic tooth movement (OTM) timing on tooth movement through alveolar bone defects treated with guided bone regeneration (GBR) utilizing xenografts (Bio-Oss) and alloplast (β-TCP).Materials and Methods:Twenty-four standard alveolar bone defects in six male beagle dogs were treated by GBR using either Bio-Oss or β-TCP (experimental), whereas the control defects were left empty. The defects were further grouped into early or late subgroups, depending on OTM timing after GBR (ie 1 month or 2 months, respectively). Rates of OTM were measured intraorally, while computed tomography scan images were used to assess bone density, alveolar bone height, second premolar displacement, and tipping tendency.Results:Generally, the Bio-Oss early and Bio-Oss late subgroups recorded the lowest amount of tooth movement compared with other modes of GBRs assessed. Before OTM, the control group registered significantly lower bone height compared with the Bio-Oss and β-TCP groups (P < .01). The control group was inferior on bone density and bone height compared with Bio-Oss and β-TCP.Conclusions:The Bio-Oss group had favorable radiologic features (higher alveolar bone level and bone density with less premolar tipping) but showed slower OTM than the control group. The late OTM subgroup had favorable radiologic features and showed faster tooth movement than the early OTM in the β -TCP group.     

Local and chronic application of PTH accelerates tooth movement in rats

We previously reported that whereas systemic continuous infusion of parathyroid hormone (PTH) accelerated orthodontic tooth movement, systemic but intermittent injection of PTH did not increase the rate of tooth movement. Analysis of these data suggested that continuous administration of PTH could be applicable for orthodontic therapy. In the present study, we investigated whether local and chronic application of PTH(1-34) would accelerate orthodontic tooth movement. To increase the residence time of PTH in the injected area, we used methylcellulose (MC) gel (2% W/V) for a slow-release formulation of PTH. MC gel containing PTH (PTH-MC) continuously released biologically active PTH into the acceptor medium for more than 72 hrs in vitro. When male rats received a local injection of PTH-MC into the subperiosteum in the mesio-palatal region of the maxillary first molar (M1) every other day, M1 movement, which was mesially drawn by an orthodontic coil spring attached to the maxillary incisors, was accelerated in a dose-dependent manner. PTH-MC injection at 1 microg/400 g body weight caused a 1.6-fold increase in the rate of tooth movement. The acceleration of tooth movement by PTH-MC injection was marked on days 6, 9, and 12. Local injection of PTH dissolved in saline without MC did not significantly accelerate tooth movement on day 6 or later. Histological examination revealed active osteoclastic bone resorption and a widened periodontal space on the compression side of the periodontal tissue in the PTH-MC-injected rats. These results suggest that local injection of PTH in a slow-release formulation is applicable to orthodontic therapy.     

M-CSF油包水型微乳对大鼠正畸牙齿移动的影响

目的探讨巨噬细胞集落刺激因子（M—CSF）油包水型（W／O）微乳对大鼠正畸牙齿移动及其牙周组织改建的影响。方法选用蓖麻油和无水乙醇分别作为表面活性剂和助表面活性剂,油酸聚乙二醇甘油酯作为油相,M-CSF水溶液为水相,制备成M—CSF油包水型微乳。加力ld开始,每2d将该微乳局部注射于大鼠左上第一磨牙,分别于1d,3d,7d,14d测量上颌第一磨牙移动距离,用HE染色观察牙周组织改建情况。结果加力1d,4组间无明显差异（P〉0．05）;加力3d,M—CSF微乳组正畸牙移动距离大于其它组,但与M—CSF水溶液组差别无统计学意义（P〉0．05）;加力7d和14d,M-CSF微乳组正畸牙移动距离同样大于其它组,差异有统计学意义（P〈0．01）,且压力侧牙槽骨骨吸收陷窝增多,呈“锯齿”状。结论大鼠正畸牙齿局部注射M．CSF油包水型微乳可以促进其移动及压力侧牙周组织改建。     

Comparative study of gene expression during tooth eruption and orthodontic tooth movement in mice

Objective:  The aim of this study was to understand tooth eruption by comparing the gene expression during tooth eruption and orthodontic tooth movement (OTM).
Materials and methods:  Orthodontic force was applied on maxillary molars for 2, 4, 7 and 14 days to study tooth movement. Mice at PN 0, 7, 10, 15 and 21 were fixed to observe tooth eruption. Comparative study of two procedures was assessed by haematoxylin and eosin, tartrate-resistant acid phosphatase staining and in situ hybridization for matrix metalloproteinase ( Mmp ) 2 , 13 , bone sialoprotein ( Bsp ) and osteocalcin ( Ocn ).
Results:  Tartrate-resistant acid phosphatase activity and expression of Mmp2 , 13 were obviously detectable in the compression region during OTM. They were also identified in the occlusal and apical region of alveolar bone during tooth eruption. Strong expression of Bsp and Ocn was detectable at the tension side during OTM. These genes were also expressed in the inner lateral region of alveolar bone adjacent to the tooth, but absent in the inner surface of the occlusal and root apical regions during tooth eruption.
Conclusion:  The process of alveolar bone metabolism during developmental eruption and OTM shares the same mechanism. Internal force, as the orthodontic force for OTM, may be initiating factor for tooth eruption.     

The effect of bone morphometric changes on orthodontic tooth movement in an osteoporotic animal model

Objective:To elucidate the effect of bone morphometric changes on orthodontic tooth movement (OTM) in zoledronic acid–treated ovariectomized rats.Materials and Methods:Twenty-one 10-week-old female Wistar rats were divided into ovariectomy (OVX), OVX with zoledronic acid administration (OVX + ZOL), and sham operation (control) groups. Two weeks after OVX, ZOL administration was initiated. Twelve weeks after OVX, a nickel-titanium closed-coil spring of 25-g force was applied mesially to the maxillary left first molar. In vivo micro–computed tomography (CT) of the left proximal tibia was performed for bone morphometric analysis every 2 weeks after OVX. In addition, OTM was investigated using micro-CT at 0, 12, and 14 weeks after OVX.Results:There were significant differences in the bone mineral content (BMC), bone volume (BV), BMC to tissue volume ratio (BMC/TV), and BV to TV ratio of trabecular bone between the control and OVX groups and also between the OVX + ZOL and OVX groups. In the OVX + ZOL group, increased BMC and BV in the cortical bone and increased bone mineral density (BMD) in the trabecular bone were observed. Interestingly, OTM in the OVX group was almost two times more than that in the control and OVX + ZOL groups. Moreover, OTM was correlated with BMD, BMC, BV, and BMC/TV in the trabecular bone.Conclusions:OVX accelerated OTM, while ZOL suppressed it. OTM demonstrated a significant negative relationship with trabecular bone mass.     

Effects of echistatin and an RGD peptide on orthodontic tooth movement

We tested whether orthodontic tooth movement (OTM) could be blocked by local administration of echistatin or an arginine-glycine-aspartic acid (RGD) peptide, agents known to perturb bone remodeling, adjacent to maxillary molars in rats. These molecules were incorporated into ethylene-vinyl acetate (ELVAX), a non-biodegradable, sustained-release polymer. In vitro experiments showed that the echistatin and RGD peptide were released from ELVAX in active forms at levels sufficient to disrupt osteoclasts. Biotinylated RGD peptide was released from ELVAX into the PDL after surgical implantation. ELVAX loaded with either RGD peptide or echistatin and surgically implanted next to the maxillary molars inhibited orthodontic tooth movement (p < 0.01). The RGD peptide also reduced molar drift (p < 0.05). This study shows the feasibility of using ELVAX to deliver integrin inhibitors adjacent to teeth to limit local tooth movement in response to orthodontic forces.     

正畸牙齿移动过程中大鼠三叉神经节CGRP mRNA表达变化

目的：观察正畸牙齿移动不同时期大鼠三叉神经节CGRP mRNA表达变化。方法：采用反转录。聚合酶链反应（RT-PCR）技术检测正畸加力和撤力后不同时期大鼠三叉神经节CGRP mRNA水平的变化。结果：加力后2h CGRP mRNA的表达量没有明显增加,至加力后8h开始增加,加力1d-1W达到最高峰,至撤力后2～4WCGRP mRNA的表达量开始下降,但CGRP mRNA水平仍然明显高于对照组（P〈0．05）。结论：CGRP可能不仅参与早期正畸牙周组织的炎症损伤过程,而且可能参与了后期的组织修复重建过程。     

骨皮质切开术通过促进成骨影响大鼠牙齿快速移动安全性的研究

目的:研究骨皮质切开术对大鼠正畸牙移动的影响及其组织学改建机制。方法:选用健康未孕雌性SD大鼠48只,随机分为骨皮质切开手术组和对照组。在手术组大鼠行骨皮质切开术,对照组大鼠行对照手术后,构建正畸牙移动模型。在牙移动0、1、3、7 d分别处死2组大鼠各6只。测量牙移动距离并制备组织学切片行HE染色、骨钙素及Runx2免疫组织化染色。采用SPSS16.0 软件包对数据进行统计分析,P<0.05为差异有显著性。结果:骨皮质切开组大鼠在移动3 d后牙移动速度大于假手术组大鼠(P<0.05)。牙移动第3天和第7天,手术组大鼠张力区新骨面积大于假手术大鼠(P<0.05),同时,此时手术组张力区骨钙素阳性成骨细胞增加(P<0.05)。手术组大鼠牙移动3 d及7 d时张力区Run2表达均高于假手术组(P<0.05)。结论:骨皮质切开术加速正畸牙移动的同时促进牙周组织成骨活性,这可能是保障牙移动安全性的关键因素。     

骨皮质切开加速大鼠正畸牙移动的机制研究

目的:研究骨皮质切开术加速大鼠正畸牙移动的组织学改建机制.方法:选用健康未孕雌性Sprague-Dawley(S-D)大鼠48只,随机分为骨皮质切开手术组和对照组.在手术组大鼠行骨皮质切开术,对照组大鼠行对照手术后,构建正畸牙移动模型.在牙移动0、1、3、7d分别处死2组大鼠各6只.测量牙移动距离并制备组织学切片,行抗酒石酸酸性磷酸酶(TRAP)染色和核因子κB受体活化因子配体(RANKL)免疫组织化学检测.采用SPSS16.0软件包对数据进行统计学分析.结果:骨皮质切开术可在牙移动第1天及3d后加速正畸牙移动,而牙移动3d时2组大鼠牙移动距离无显著差异.牙移动第3天和第7天,手术组大鼠压力区破骨细胞数目均显著高于对照组(P＜0.05),手术组压力区RANKL的表达也显著高于对照组.结论:骨皮质切开术可加速大鼠正畸牙移动,这可能是由于牙周组织中RANKL高表达介导的破骨增强所致.