MEPE expression in osteocytes during orthodontic tooth movement

MEPE and DMP1 may play a role in mineralisation and demineralisation within the osteocyte microenvironment. Our earlier studies showed that DMP1 is mechanically responsive [Gluhak-Heinrich J, Ye L, Bonewald LF, Feng JQ, MacDougall M, Harris SE, et al. Mechanical loading stimulates dentin matrix protein 1 (DMP1) in osteocytes in vivo. J Bone Min Res 2003;18(5):807-17]. OBJECTIVES: To examine the effect of mechanical loading on the expression of MEPE using mouse tooth movement model, and compare this effect to that on DMP1. METHODS: In situ hybridisation and immunohistochemistry was performed on 38 treated and 38 control bone sites loaded 6-72 h. ImageJ was used for quantification of mRNA expression in osteocytes. RESULTS: Alveolar osteocytes showed high basal level of MEPE that decreased during the first day of loading, followed by 2.8-fold stimulation at day 3, and returning to a control level by day 7. CONCLUSION: The osteocyte specific mechanical stimulation of MEPE was delayed and different, compared to that of DMP1. This suggests a distinct role of MEPE and DMP1 in the response of osteocytes to mechanical loading in vivo.     

The role of osteocytes during experimental orthodontic tooth movement: A review

ObjectiveTo explore the types of orthodontic force-induced mechanical stimuli that regulate osteocyte function.DesignIn orthodontics, a tooth can be moved through the alveolar bone when an appropriate orthodontic force is applied. These mechanical loads stimulate cells within the bone tissue around the tooth. These cellular responses lead to bone resorption on the side of the tooth where the pressure has been applied and bone deposition on the side of the tooth experiencing tension. Recently, osteocytes were identified to function as mechano-sensory cells in bone tissue that direct bone resorption and bone formation. Based on recent literature, the proposed function of osteocytes during orthodontic tooth movement is explored with better understanding.ResultsSeveral stimuli regulating osteocyte function have been highlighted, and their potential roles in events initiating osteocyte sensing of orthodontic force have been explored in detail. The most popular hypotheses for osteocyte response include stress-induced bone matrix deformation/microcrack formation and fluid-flow shear stress.ConclusionsUnderstanding osteocyte function under mechanical stress may have profound implications in future orthodontic treatments.     

正畸牙移动过程中破骨细胞出现区应力特点的三维有限元法分析

目的探讨大鼠磨牙近中倾斜移动时破骨细胞出现区的应力特点。方法大鼠上颌第一磨牙在40g、100g力作用2周后，制作连续牙周切片，进行组织学观察，同时建立其三维有限元模型，将组织切片与应力分布的结果对比观察，分析牙周膜内破骨细胞出现区的应力特点。结果无论100g还是40g力作用下，破骨细胞出现频数最高区域的最小主应力(Min)以及应力在牙齿移动方向上的分量(S11)均在一个较小应力范围内，而Max、Von Mises应力则无此现象。同一力作用下破骨细胞出现区的应力仅S11不随牙根不同部位的变化而变化。结论大鼠磨牙倾斜移动时破骨细胞出现与牙齿移动方向上的应力分量、最小主应力分布有着密切的联系。     

Effects of different types of tooth movement and force magnitudes on the amount of tooth movement and root resorption in rats

Objective:To investigate differences in the amount of tooth movement and root resorption that occurred after tipping and bodily movement of the maxillary first molar in rats.Materials and Methods:Ten-week-old female Wistar rats were divided into two groups according to type of tooth movement and subdivided into four subgroups according to the magnitude of applied force. Nickel-titanium closed-coil springs exerting forces of 10, 25, 50, or 100 g were applied to the maxillary left first molars to induce mesial tooth movement. We designed a novel orthodontic appliance for bodily tooth movement. Tooth movement distance and root resorption were measured using microcomputed tomography and scanning electron and scanning laser microscopy.Results:The amount of tooth movement in the bodily tooth movement group was less than half that in the tipping tooth movement group. The greatest amount of tooth movement occurred in the 10-g tipping and 50-g bodily tooth movement subgroups, and the amount of tooth movement decreased with the application of an excessive magnitude of force. Conversely, root resorption increased when the heavier orthodontic force was applied in both groups. Root resorption in the tipping tooth movement group was approximately twice that in the bodily tooth movement group.Conclusions:Root resorption in the tipping tooth movement group was more pronounced than that in the bodily tooth movement group. Although the amount of tooth movement decreased when extremely heavy forces were applied, root resorption increased in both the tipping and bodily tooth movement groups in rats.     

Tissue responses resulting from tooth movement surgically assisted by corticotomy and corticision in rats

Objective:To compare the histological responses in corticotomy- and corticision-assisted tooth movement.Materials and Methods:Ninety Wistar rats were divided into three groups: C (control—tooth movement only), CT (tooth movement + corticotomy), and CI (tooth movement + corticision). Surgeries were performed on the vestibular and lingual cortical bone of the maxillary first molar. Tooth movement was carried out with nickel-titanium closed coil springs having a force of 30 g. The rats were sacrificed at 3, 14, and 28 days. To evaluate the number of osteoclasts and amount of root resorption, a tartrate-resistant acid phosphatase stain was used. Hematoxylin and eosin staining was performed for areas of hyalinization, and the organic bone matrix was stained with picrosirius.Results:The CT group showed a greater number of osteoclasts than did the C group on day 3 (P < .05). At the same time point, the CT and CI groups showed a delayed onset of organic bone matrix remodeling and a lower incidence of root resorption than did the C group (P < .05). There were also fewer hyalinization areas in the CI group than in the C group on day 3 (P < .05).Conclusions:Corticotomy effectively increased bone resorption during the early stages of tooth movement, but this increase was not observed for corticision. The surgical procedures did not accelerate organic bone matrix remodeling. Corticotomies and corticisions decreased the risk of root resorption only during the early stages of movement. Corticision reduced the level of hyalinization, while corticotomy did not.     

Osteocyte death during orthodontic tooth movement in mice

Objective:To investigate the time course of osteocyte death in a mouse model of orthodontic tooth movement (OTM) and its association to the caspase-3 activation pathway and osteoclast formation.Materials and Methods:Twenty-five male wild type CD-1 mice (8–12 weeks old) were loaded with an orthodontic appliance. A spring delivering 10–12 g of force was placed between the right first molar and the incisor to displace the first molar mesially. The contralateral unloaded sides served as the control. The animals were equally divided into five different time points: 6, 12, 24, and 72 hours and 7 days of orthodontic loading. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, caspase-3 immunostaining, and tartrate-resistant acid phosphatase (TRAP) staining was performed on histologic sections of the first molars. The labeling was quantified in osteocytes on the compression side of the alveolar bone at each time point.Results:TUNEL labeling significantly increased at 12, 24, and 72 hours after orthodontic loading; the peak was observed at 24 hours. Elevated caspase-3 labeling was noted at 12, 24, and 72 hours and 7 days after loading, although the increase was not significant. Significant osteoclast formation was initially evident after 72 hours and progressively increased up to 7 days.Conclusions:Osteocyte death during OTM peaks at 24 hours, earlier than initial osteoclast activation. However, only a slight trend for increased caspase-3 activity suggests that other mechanisms might be involved in osteocyte death during OTM.     

糖尿病大鼠正畸牙齿移动及组织学变化

目的 探讨糖尿病大鼠正畸牙移动对牙周组织的影响。方法 选用80只雄性SD大鼠，牵引左上颌第一磨牙近中移动。实验组以STZ腹腔注射制备Ⅰ型糖尿病模型，对照组注射柠檬酸缓冲液，3周后开始实验。分别在加力0、3、7、14、21天处死大鼠，记录上颌第一磨牙移动距离，组织HE染色后，观察牙周组织形态学的改变。结果 ①实验组大鼠牙齿移动距离在移动末期明显大于对照组；②实验组骨质疏松；③实验组大鼠压力侧破骨细胞数在骨吸收期少于对照组，3、7、14天有统计学意义；④实验组大鼠在骨形成期张力侧成骨细胞数少于对照组，14、21天有统计学意义。结论 ①糖尿病性骨质疏松导致正畸牙齿移动末期牙齿移动速度加快；②糖尿病骨质反应能力降低，牙齿移动过程中破骨活动和成骨过程均受抑制。     

IGF-I, IGF-IR and IRS1 expression as an early reaction of PDL cells to experimental tooth movement in the rat

Objective

To characterize in vivo the role of IGF-I and its signalling, as an early reaction in the mechanotransduction process and to analyse changes of the local expression related to the magnitude of the applied force.

Materials and methods

Forces of 0.1 N, 0.25 N and 0.5 N were applied to move the right upper first molars of 12 anaesthetized rats mesially. These forces were kept constant for 4 h. The untreated contralateral side served as a control. Paraffin-embedded sections of the resected jaws were prepared for immunohistochemistry to localize insulin-like growth factor-I (IGF-I), its receptor (IGF-IR), and insulin receptor substrate 1 (IRS1). Histomorphometric analysis was performed to count the percentage of immunoreactive cells in different parts of the periodontal ligament.

Results

IGF-I, IGF-IR and IRS1 positive cells were observed in the periodontal tissues of the control and loaded teeth. In the experimental group, the number of IGF-I-, IGF-IR- and IRS1-positive cells increased significantly on the tension side and decreased on the compression side.

Conclusions

These data indicate a close relationship between mechanical loading of the PDL and the autocrine/paracrine expression of IGF components as an early step in the mechanotransduction process leading in the long term to an organized remodelling of the alveolar bone.     

牙齿移动对大鼠动情周期和雌激素水平的影响

目的探讨正畸施力时间对雌性大鼠动情周期的影响。方法200只雌性大鼠均分为对照组、加力1次组、加力4次组、假处理1次组和假处理4次组。各组均分为4个亚组，在动情周期不同时段进行相应处理。测定雌激素含量，记录动情周期变化。结果在同一动情周期时段加力的各亚组之间，雌激素测量值的差异有统计学意义（P〈0．01）；在同一处理方式下各亚组之间，雌激素测量值的差异也有统计学意义（P〈0．05）。结论加力对动情后期和间期加力组大鼠的动情周期有影响。选择在动情期戴入矫治装置及加力，可减少加力对雌性大鼠的不利影响。     

辛伐他汀抑制正畸牙齿移动后复发距离的实验研究

目的探讨全身给予辛伐他汀对大鼠实验性牙移动后牙齿复发距离的影响。方法选用32只雄性Wistar大鼠，随机分成4组：对照组（生理盐水）、低剂量组（2．5mg／kg）、中剂量组（5．0mg／kg）、高剂量组（10．0mg／kg），牵引其上颌第一磨牙向近中移动。实验组在加力装置去除前1天开始，腹膜下注射辛伐他汀，对照组注射生理盐水，每日1次，连续4周。分别在加力装置去除时及其后1周、4周，测量上颌第一、第二磨牙间距离，测量体重。结果①各组大鼠体重无明显变化（P〉0．05）。②低、中、高剂量组大鼠牙齿移动复发距离小于对照组（P〈0．05）、复发百分率明显低于对照组（P〈0．01），且剂量越小复发程度越小，低剂量组复发百分率最低。结论辛伐他汀能有效地抑制实验性牙移动后牙齿复发的程度，低剂量时效果最明显。     

正畸牙齿移动时骨形成蛋白变化的实验研究

目的：探讨正畸虎齿移动过程中骨形成蛋白（bone morphogenetic protein BMP)的分布,表面的变化,方法：采用MBP单克隆抗体免疫 化染色及计算机图像分析的方法对实验性兔正畸牙齿移动牙周组织中BMP的表达变化进行了定性,定量分析,结果：正畸牙齿移动过程中,张力区牙周膜BMP达高峰出现早于牙槽骨表面,与张力区比较,压力区BMP表达高峰出现较迟,结论：BMP参与正畸牙齿移动时的骨吸收和骨增生的骨改建过程,并发挥着重要的作用。     

牙槽骨缺损修复对牙齿移动影响的动物实验

目的了解大鼠牙齿在牙槽骨缺损修复区的移动情况。方法选择40只大鼠，造成一侧牙槽骨缺损，填入45％二氧化硅、24．5％氧化钠、24．5％氧化钙和6％五氧化二磷，作为修复侧，另一侧作为对照侧。术后14周用0．39N力牵引双侧第一磨牙近中移动。配对t检验比较牵引8周后双侧磨牙的移动距离和牙周膜宽度。结果36只大鼠两侧第一磨牙的平均移动距离、牙周膜宽度的差异均无统计学意义（P〉0．05）。结论牙槽骨缺损修复侧可以进行正畸牙齿移动，修复侧的牙齿移动距离及牙周组织受正畸力后的改建情况，均与对照侧无显著差别。     

牵张成骨后牵张新骨中牙移动的实验研究

目的:比较牵张成骨后牵张新骨中不同时间点牙移动的异同,探讨牵张成骨后牙移动的最佳时机.方法:以8 只beagle犬为实验对象,I组为牵张成骨后第2周进行牙移动,II组为牵张成骨后第6周进行牙移动.应用实体测量、X线片、HE染色等方法,对移动牙的牙根、牙周以及牙槽骨的情况进行分析.结果:在牵张成骨后第2周和第6周用相同的力值将牙齿往新骨区牵引,第三前磨牙与第四前磨牙之间的距离随时间推移而减小,组内差异具有统计学意义(P<0.05),牵张成骨后第2周与第6周2 组之间差异有统计学意义(P<0.05).结论:在相同力值下,牵张成骨后第2周开始牙移动的速度要比第6周快,但第2周移动牙的牙周吸收较第6周的严重.     

大鼠正畸牙移动中Osterix的表达

目的：通过观察大鼠正畸牙移动过程中牙周膜内转录因子Osterix（Osx）的表达,初步探讨Osx与正畸矫治过程中牙周组织改建的关系。方法：将54只雄性SD大鼠随机分为9组,每组6只,即正畸加力0、3、6、12、24 h和3、5、7、14 d组,以右侧上颌第一磨牙不加力为自身对照组,左侧上颌第一磨牙为实验组,使用自制的加力装置移动磨牙并制备组织标本。SABC免疫组织化学法检测实验性大鼠正畸牙齿移动过程中牙周组织Osx的表达。结果：对照组大鼠牙周组织中Osx低表达,实验组于加力5 d时Osx表达水平达到最高,且张力区整体上比压力区阳性染色深。结论：正畸力作用下Osx参与牙周组织的改建,是正畸成骨的调控途径之一。     

MMP-3及TIMP-1在正畸牙周组织改建过程中的表达

目的：探讨大鼠正畸牙周组织改建过程中基质金属蛋白酶－３（ＭＭＰ－３）和金属蛋白酶组织抑制因子－１（ＴＩＭＰ－１）与正畸牙齿移动的关系。方法：在ＳＤ成年大鼠上颌左侧第一磨牙上颌切牙之间安置正畸装置,建立大鼠上移动实验模型。于牙齿移动１、３、５、７、１４ｄ后取材分别进行免疫组化染色,图像分析,观察ＭＭＰ－３和ＴＩＭＰ－１表达的变化。结果：牙齿移动１ｄ后,牙周组织细胞ＭＭＰ－３表达增强,５ｄ后ＭＭＰ－３     

Correlation between pain and hyalinization during tooth movement induced by different types of force

Objectives:To evaluate the correlation between pain and tissue reactions during induced tooth movement (ITM).Materials and Methods:Forty-two male Wistar rats (Rattus norvegicus; ∼90 days of age, 300 g) were used. The animals were divided into seven groups of six rats each: one control group and six experimental groups subjected to ITM by continuous force (CF) or interrupted continuous force (ICF) for 1, 3, and 5 days. Hyalinization of the periodontal ligament (PL) and occurrence of pain were observed. Animal behavior (walking, climbing, immobile posture, resting/sleeping, and directed face grooming) and the presence of chemical mediators associated with nociception, cyclooxygenase-2 (COX-2), and interleukin-1 beta (IL-1β) in the PL were analyzed.Results:There was a moderate positive correlation between hyalinization and the presence of COX-2 (r_s = 0.404; P < .05) and IL-1β (r_s = 0.429; P < .05). There was a moderate negative correlation between hyalinization and exploratory behaviors (walking, r = −0.586, P < .01; climbing, r = −0.573, P < .01), and a moderate positive correlation between hyalinization and resting/sleeping (r = 0.467; P < .01).Conclusions:The results suggest a correlation between pain and undesirable tissue reactions in ITM.     

Effects of pulsed electromagnetic field vibration on tooth movement induced by magnetic and mechanical forces: a preliminary study

BACKGROUND: This study was designed to determine whether or not high-frequency and low-magnitude vibration affects orthodontic tooth movement caused by magnetic or/and mechanical forces. METHODS: Forty-four 7-week-old Wistar rats were randomly divided into four groups, with each group further divided into experimental and control subgroups. Neodymium-Iron-Boron (Nd-Fe-B) magnets and Sentalloy closed coil springs were placed between maxillary or mandibular first molars and incisors to activate tooth movement. The animals of experimental subgroups were exposed to the vibration induced by pulsed electromagnetic fields (PEMF) whilst the control subgroups were under normal atmosphere. The experiment lasted for 14 days and all of the animals were sacrificed for examination. The changes in the space between the molar and incisor were measured to indicate the amount of tooth movement. RESULTS: The coil springs, either with sham or active magnets, move molar much more than magnets alone, regardless of absence or presence of PEMF (p < 0.001). Under PEMF, the coil spring moved significantly more amount of tooth movement than that of coil-magnet combination (p < 0.01), as did the magnets compared to sham magnets (p < 0.019). Under a non-PEMF scenario, there was no significant difference in tooth movement between coil spring and coil-magnets combination, nor was there difference between magnets and sham magnets. CONCLUSIONS: It is suggested that the PEMF-induced vibration may enhance the effect of mechanical and magnetic forces on tooth movement.     

Human tooth movement in response to continuous stress of low magnitude.

Conventional orthodontic therapy often uses force magnitudes in excess of 100 g to retract canine teeth. Typically, this results in a lag phase of approximately 21 days before tooth movement occurs. The current project was undertaken to demonstrate that by using lower force magnitudes, tooth translation can start without a lag phase and can occur at velocities that are clinically significant. Seven subjects participated in the 84-day study. A continuous retraction force averaging 18 g was applied to 1 of the maxillary canines, whereas a continuous retraction force averaging 60 g was applied to the other. The magnitude was adjusted for each canine to produce equivalent compressive stresses between subjects. Estimated average compressive stress on the distal aspect of the canine teeth was 4 kPa or 13 kPa. The moment-to-force ratios were between 9 and 13 mm. Tooth movement in 3 linear and 3 rotational dimensions was measured with a 3-axis measuring microscope and a series of dental casts made at 1- to 14-day intervals. The results showed a statistical difference in the velocity of distal movement of the canines produced by the 2 stresses (P =.02). The lag phase was eliminated and average velocities were 0.87 and 1.27 mm/month for 18 and 60 g of average retraction force. Interindividual velocities varied as much as 3 to 1 for equivalent stress conditions. It was concluded that effective tooth movement can be produced with lower forces and that because loading conditions were controlled, cell biology must account for the variability in tooth velocities measured in these subjects.