Probiotics ameliorate alveolar bone loss by regulating gut microbiota

ObjectivesOestrogen deficiency is an aetiological factor of postmenopausal osteoporosis (PMO), which not only decreases bone density in vertebrae and long bone but also aggravates inflammatory alveolar bone loss. Recent evidence has suggested the critical role of gut microbiota in osteoimmunology and its influence on bone metabolisms. The present study aimed to evaluate the therapeutic effects of probiotics on alveolar bone loss under oestrogen‐deficient condition.Materials and MethodsInflammatory alveolar bone loss was established in ovariectomized (OVX) rats, and rats were daily intragastrically administered with probiotics until sacrifice. Gut microbiota composition, intestinal permeability, systemic immune status and alveolar bone loss were assessed to reveal the underlying correlation between gut microbiota and bone metabolisms.ResultsWe found administration of probiotics significantly prevented inflammatory alveolar bone resorption in OVX rats. By enriching butyrate‐producing genera and enhancing gut butyrate production, probiotics improved intestinal barrier and decreased gut permeability in the OVX rats. Furthermore, the oestrogen deprivation‐induced inflammatory responses were suppressed in probiotics‐treated OVX rats, as reflected by reduced serum levels of inflammatory cytokines and a balanced distribution of CD4⁺IL‐17A⁺ Th17 cells and CD4⁺CD25⁺Foxp3⁺ Treg cells in the bone marrow.ConclusionsThis study demonstrated that probiotics can effectively attenuate alveolar bone loss by modulating gut microbiota and further regulating osteoimmune response and thus represent a promising adjuvant in the treatment of alveolar bone loss under oestrogen deficiency.     

淫羊藿苷对大鼠正畸牙齿压力区牙周组织RANKL和Wnt3a表达的影响

目的:观察不同剂量的淫羊藿苷对大鼠正畸牙齿移动时压力区牙周组织中RANKL和Wnt3a表达的影响。方法:将24只健康雄性SD大鼠随机分为4组,根据淫羊藿苷灌胃的剂量分为生理盐水组(对照组)、1 mg/kg淫羊藿苷组、3 mg/kg淫羊藿苷组、5mg/kg淫羊藿苷组(实验组),使用50 g力近中移动左侧上颌第一磨牙。通过免疫组化方法检测压力区牙周组织中RANKL和Wnt3a蛋白的表达。结果:生理盐水组上颌第一磨牙压力区牙根和牙槽骨表面粗糙,牙周膜间隙变窄,可见骨吸收陷窝和破骨细胞,不同剂量淫羊藿苷组牙周膜间隙趋于恢复正常,骨吸收陷窝出现明显减少。RANKL和Wnt3a在生理盐水组和淫羊藿苷组的压力区牙周组织中都有表达。与生理盐水组比较,不同剂量淫羊藿苷组压力区牙周组织中RANKL的表达均显著降低,Wnt3a的表达均明显增加,且RANKL的表达随淫羊藿苷剂量的增加而逐渐减少(P0.05),Wnt3a的表达随淫羊藿苷剂量的增加明显增加(P0.05)。结论:不同剂量淫羊藿苷能减少正畸时牙齿移动过程中压力区牙周组织中RANKL的表达,增加Wnt3a的表达,且作用与其剂量具有一定的相关性。     

Distribution of 3H-proline within transseptal fibers of the rat following release of orthodontic forces

Maxillary right first molar teeth of rats were tipped mesially with an orthodontic appliance for 2 weeks (experimental group), 3H-proline was injected, and orthodontic forces were removed 6 hr later (time 0). The contralateral molar teeth of treated (internal control group) and age- and weight-matched untreated animals (external control group) were also studied. Diastemata were created between the molar teeth by the orthodontic appliance, and transseptal fibers between first and second (P less than 0.001) and second and third molars (P less than 0.005) were significantly lengthened as compared to external and internal controls at time 0. Diastemata between molar teeth were closed 5 days after removal of orthodontic force. Transseptal fibers adjacent to the source of the orthodontic force (mesial region) had the highest mean number of 3H-proline-labeled proteins at time 0 and at all times following removal of the force (P less than 0.001), and had the highest rate of labeled protein removal (P less than 0.001). Half-lives for removal of 3H-proline-labeled transseptal fiber proteins were significantly greater in mesial and distal regions and significantly less in middle regions of experimentals than in corresponding regions of external controls (P less than 0.001). These data suggest the following: 1) transseptal fibers adjust their length by rapid remodeling in regions experiencing a tensile force; 2) collagenous protein turnover within the middle third of the transseptal fibers is more rapid subsequent to release of orthodontic force than during normal physiologic drift, suggesting that this region adapts rapidly to changes in adjacent tooth position and that these fibers do not play a significant role in relapse of orthodontically relocated teeth; and 3) significant differences in turnover rates of 3H-proline-labeled transseptal ligament proteins of external and internal control quadrants suggest that tooth movement produces both local and systemic effects on collagenous protein metabolism.     

Microdamage in porcine alveolar bone due to functional and orthodontic loading

Bone remodelling has been associated with microdamage. The aim of this study was to investigate the presence of microdamage in the alveolar bone and its potential role in the initiation of bone remodelling following the application of an orthodontic load. The three-dimensional morphology of the alveolar bone was investigated by means of high resolution micro-CT scanning. In 25, 3-month-old, male Danish land-race pigs, the alveolar bone around the lower right and left first molars was analysed. The right first molar was moved buccally with a force of 130 cN by means of a custom-made cantilever made of a TMA 0.017 x 0.025 inch wire. The left molar was left untreated. After 1, 2, 4, 7 and 15 days of treatment the regions containing the right and left molars were excised and en bloc stained in basic fuchsin and the presence of microdamage detected. Diffuse damage was present in the alveolar bone of both the treated and the untreated teeth on both sides. On the lingual sides, diffuse damage showed the same orientation as the periodontal fibres. Bone microcracks were also detected on both the treated and untreated teeth. On the buccal surfaces they where often observed in close proximity to scalloped resorption surfaces. After 1 day of treatment, the presence of microcracks on the buccal-treated side was particularly marked. To conclude, bone microdamage is present in porcine alveolar bone in form of both microcracks and diffuse damage, suggesting that microdamage-driven remodelling also occurs in the alveolar bone. The presence of bone microcracks in the direction of the orthodontic force at day 1 suggests that they could represent the first damage induced by the orthodontic load that has to be repaired.     

Strain-dependent up-regulation of ephrin-B2 protein in periodontal ligament fibroblasts contributes to osteogenesis during tooth movement

During orthodontic tooth movement, the application of adequate orthodontic forces allows teeth to be moved through the alveolar bone. These forces are transmitted through the periodontal ligaments (PDL) to the supporting alveolar bone and lead to deposition or resorption of bone, depending on whether the tissues are exposed to a tensile or compressive mechanical strain. Fibroblasts within the PDL (PDLF) are considered to be mechanoresponsive. The transduction mechanisms from mechanical loading of the PDLF to the initiation of bone remodeling are not clearly understood. Recently, members of the ephrin/Eph family have been shown to be involved in the regulation of bone homeostasis. For the first time, we demonstrate that PDLF exposed to tensile strain induce the expression of ephrin-B2 via a FAK-, Ras-, ERK1/2-, and SP1-dependent pathway. Osteoblasts of the alveolar bone stimulated with ephrin-B2 increased their osteoblastogenic gene expression and showed functional signs of osteoblastic differentiation. In a physiological setting, ephrin-B2-EphB4 signaling between PDLF and osteoblasts of the alveolar bone might contribute to osteogenesis at tension sites during orthodontic tooth movement.     

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.     

Predictive factors for alveolar fenestration and dehiscence

The purpose of this study was to evaluate the distribution and incidence of two forms of alveolar bone resorption known as fenestration and dehiscence across time and space. To accomplish this a Medieval French population was studied and the results were compared with other studies to examine incidence and distribution of alveolar bone resorption. Thus, 1175 teeth were analysed for 81 individuals, from an agropastoral Medieval (12th–14th century) archaeological site of Vilarnau located in the South of France. Tooth presence and absence as well as dental alveolar resorption were recorded. A new standardised methodological approach to record alveolar resorption is presented and can be used for any skeletonised series. Measurements of dehiscence were made in the midline on each root in relation to the cemento-enamel junction and fenestration was considered as resorption restricted to alveolar bone. Through analyses of the distribution and incidence of alveolar bone resorption over-time in a Medieval French population, along with nine other studies, we present a list of predictive factors for alveolar bone resorption. Among these factors tooth position and function were the most important; anterior teeth were more commonly affected, bone resorption was more common on the labial/buccal versus palatal/lingual surfaces, fenestration was also more common on the maxilla and dehiscence on the mandible (p ≤ 0.001). These patterns do not vary through time or space, and therefore, provide predictive factors for health practitioners in oral therapy to improve patient recovery and post oral treatment success.     

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     

Interdental distraction osteogenesis and rapid orthodontic tooth movement: a novel approach to approximate a wide alveolar cleft or bony defect

The closure of a wide alveolar cleft and fistula in cleft patients and the reconstruction of a maxillary dentoalveolar defect in traumatic patients are challenging for both orthodontists and surgeons. This is due to the difficulty in achieving complete closure by using local attached gingiva and the great volume of bone required for the graft. In this article, the authors propose using interdental distraction osteogenesis to create a segment of new alveolar bone and attached gingiva for the complete approximation of a wide alveolar cleft/fistula and the reconstruction of a maxillary dentoalveolar defect. They performed this procedure on one patient with a traumatic maxillary dentoalveolar defect and 10 patients with unilateral or bilateral cleft lips and palates who had varied dentoalveolar clefts/fistulas. Interdental and maxillary osteotomies were performed on one side of the dental arch by the cleft or defect. After a latency period of 3 days, the osteotomized distal segment of the dental arch was then distracted and transported toward the cleft or defect by using a toothborne intraoral distraction device. The alveoli and gingivae on both ends of the cleft or defect were approximated after distraction osteogenesis. The need for extensive alveolar bone grafting was eliminated. A segment of new edentulous alveolus and attached gingiva was created interdentally at a site distant to the cleft or defect. In the cleft patients, teeth were moved orthodontically into the regenerate (newly formed alveolar bone) dental crowding 1 week after distraction. The orthodontic tooth movement was rapidly completed in 3 months, and the edentulous space was eliminated. Interdental distraction osteogenesis minimizes an alveolar cleft/fistula and helps reconstruct a maxillary dentoalveolar defect by approximating the native alveoli and gingivae; it also creates new alveolar bone and gingiva for rapid 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.     

Extracellular matrix-mediated tissue remodeling following axial movement of teeth.

Tooth eruption is a multifactorial process involving movement of existing tissues and formation of new tissues coordinated by a complex set of genetic events. We have used the model of the unopposed rodent molar to study morphological and genetic mechanisms involved in axial movement of teeth. Following extraction of opposing upper molars, lower molars supererupted by 0.13 mm. Labeled tissue sections revealed significant amounts of new bone and cementum apposition at the root apex of the unopposed side following supereruption for 12 days. Newly apposited cementum and alveolar bone layers were approximately 3-fold thicker in the experimental vs the control group, whereas periodontal ligament width was maintained. Tartrate-resistant acid phosphatase staining indicated bone resorption at the mesial alveolar walls of unopposed molars and provided in tandem with new bone formation at the distal alveolar walls an explanation for the distal drift of molars in this model. Microarray analysis and semiquantitative RT-PCR demonstrated a significant increase in collagen I, integrin beta5, and SPARC gene expression as revealed by comparison between the unopposed molar group and the control group. Immunohistochemical verification revealed increased levels of integrin beta5 and SPARC labeling in the periodontal ligament of the unopposed molar. Together our findings suggest that posteruptive axial movement of teeth was accomplished by significant formation of new root cementum and alveolar bone at the root apex in tandem with upregulation of collagen I, integrin beta5, and SPARC gene expression.     

Micro-CT监测尼古丁对大鼠正畸牙移动过程中牙周改建的影响

目的:探讨不同摄取量的尼古丁对大鼠正畸过程牙周改建的影响。方法:选择120只雄性Wistar大鼠并将其随机分为四组:A组-空白对照,B组-正畸模型,C组-正畸并0.01 mg/m L尼古丁给药,D组-正畸并1 mg/m L尼古丁给药。分别于实验开始后第1、3、7、14、21天通过Micro-CT和HE染色观察模型牙齿移动距离和牙周组织改变并通过ELISA实验检测IL-17的表达。结果:Micro-CT扫描显示:正畸建模组相对于空白对照组在牙移动距离、骨体积分数、骨密度等指标均有明显变化,变化最大幅度发生在D组,B、C两组之间的差异没有统计学意义(P0.05)。21天,D组移动距离达到0.80±0.06 mm,明显高于B、C组(P0.05)。相较于空白对照组(A组),B、C、D三组Micro-CT测量的骨体积分数、骨密度、骨小梁厚度均降低,D组骨密度值降至1108.36±8.86mg/cm3。HE染色结果显示:D组在21天时破骨细胞增多并出现牙根吸收陷窝伴牙周膜纤维排列混乱;ELISA检测显示B、C组IL-17的含量在第7天时达到峰值,D组则在14天含量最高。结论:高浓度的尼古丁可加速正畸牙齿的移动速度及牙槽骨吸收,增加牙周组织中的破骨细胞及IL-17表达水平。     

New information on cranial and dental features of the Triassic archosauriform reptile Euparkeria capensis

The course of the nasolacrimal duct, interdental plate morphology, and most details of tooth and denticle morphology have not previously been described in non–archosauriform reptilkes. Here I describe these details in the Triassic archosauriform Euparkeria capensis. The nasolacrimal canal opens orbitally via a pair of foramina between the lacrimal and prefrontal. The canal arches over the antorbital fenestra, as in archosaurs. The term ‘interdental unit’ is introduced for the unit composed of an interdental septum and its accompanying interdental plate. There is no demarcation between interdental plate and septum in E. capensis. The interdental units are heavily pitted on exposed surfaces. Like teeth, they are implanted in the dental groove and are separate from the surrounding bone and from each other. They are well positioned to serve as spacers between teeth, and to resist sagittal forces on teeth during prey capture. The teeth of E. capensis are labiolingually compressed, except for the nearly conical premaxillary teeth and mesialmost dentary tooth. Lateral teeth are serrated on mesial and distal keels. The denticles are low, rounded, and separated by grooves, and are slightly larger on the distal keel. Tooth morphology suggests carnivorous habits for Euparkeria.     

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.     

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.     

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.     

丁香油酚在牙槽骨组织中的骨保护作用评价

绝经后雌激素缺乏会引起牙槽骨质流失、重塑和炎症。丁香油酚是一种酚类化合物,在牙科应用广泛并具有抗炎特性。在本研究中,以卵巢切除的大鼠为模型,服用不同剂量丁香油酚(2mg·kg-1·d-1和4mg·kg-1·d-1)12周(卵巢切除组),研究丁香油酚在牙槽骨组织中的骨保护作用。使用ELISA法检测血清中骨代谢标记物和促炎细胞因子,使用高分辨率微型计算机断层摄影术(CT)扫描牙槽骨形态,并进行骨组织学分析(H&E染色)。研究结果表明,丁香油酚不会增加卵巢切除大鼠体重和延缓子宫萎缩。由丁香油酚处理的卵巢切除大鼠的骨代谢标志物和炎性细胞因子含量显著提高,特别是高剂量组。丁香油酚的处理显著减弱了牙槽骨的形态测量变化,改善了牙槽吸收功能和牙龈渗透。卵巢切除大鼠的牙槽骨由于丁香油酚处理得到改善,炎性细胞因子表达降低。本研究初步结论表明,丁香油酚可以防止卵巢切除动物实验性诱导的牙槽骨损失,具有抗炎作用,对牙槽骨组织具有保护作用。     

利塞膦酸钠对去卵巢大鼠正畸牙齿移动期间破骨细胞中FAK蛋白表达的影响

目的:探讨利塞膦酸钠对去卵巢大鼠正畸牙齿移动期间破骨细胞中FAK蛋白表达的影响。方法:将30只雌性大鼠随机分为3组:假手术组、VOX组(卵巢切除+等量注射生理盐水)和利塞膦酸钠治疗组(切除卵巢+每3天腹膜内注射利塞膦酸钠),各10只。通过数字卡尺测量牙齿移动距离。通过蛋白质印迹检测FAK、I型胶原和整合素-β1蛋白表达水平。使用EXA-3000双能X射线BMD测量仪,测量左股骨BMD。通过RT-qPCR检测TRACP、RANKL和BMP-2 mRNA表达水平。结果:第1~3月时,与假手术组相比,VOX组大鼠体重和牙齿移动距离均增加(P<0.05),而与VOX组相比,利塞膦酸钠治疗组大鼠体重和牙齿移动距离均降低(P<0.05)。与假手术组相比,VOX组FAK、I型胶原和整合素-β1蛋白表达水平、tBMD、pBMD、mBMD和dBMD值以及TRACP、RANKL和BMP-2 mRNA水平均显著降低(P<0.05),而与假手术组和VOX组相比,利塞膦酸钠治疗组以上指标均显著增加(P<0.05)。结论:利塞膦酸钠通过调控整合素-β1/FAK信号通路,对去卵巢大鼠的骨吸收、骨质流失和骨强度降低有有效的抑制作用,可以预防和抑制卵巢切除引起的骨质疏松症的作用,这为骨质疏松症的临床治疗提供了新的依据。     

Effects of alendronate on tooth eruption and molar root formation in young growing rats

Tooth eruption consists of the movement of teeth from the bony crypt in which they initiate their development to the occlusal plane in the oral cavity. Interactions between the tooth germ and its surrounding alveolar bone occur in order to offer spatial conditions for its development and eruption. This involves bone remodeling during which resoption is a key event. Bisphosphonates are a group of drugs that interfere with the resorption of mineralized tissues. With the purpose of investigating the effects of sodium alendronate (a potent bisphosphonate inhibitor of osteoclast activity) on alveolar bone during tooth development and eruption, we gave newborn rats daily doses of this drug for 4, 14, and 30 days. Samples of the maxillary alveolar process containing the tooth germs were processed for light, transmission, and scanning electron microscopy and were also submitted to tartrate-resistant acid phosphatase histochemistry and high-resolution colloidal-gold immunolabeling for osteopontin. Inhibition of osteoclast activity by sodium alendronate caused the absence of tooth eruption. The lack of alveolar bone remodeling resulted in primary bone with the presence of latent osteoclasts and abundant osteopontin at the interfibrillar regions. The developing bone trabeculae invaded the dental follicle and reached the molar tooth germs, provoking deformities in enamel surfaces. No root formation was observed. These findings suggested that alendronate effectively inhibited tooth eruption by interfering with the activation of osteoclasts, which remained in a latent stage. This work was supported by grants from Fapesp (04/05831-9 and 06/60094-5) and CNPq (Brazil).     

In vitro effect of KCA-098, a derivative of coumestrol,on bone resorption of fetal rat femurs

The effects of 3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinoline-6-one (KCA-098), a derivative of coumestrol, on bone resorption was studied in organ cultures of 20-day fetal rat femora. KCA-098 increased the length, dry weight, and calcium and phosphorus contents of parathyroid hormone (PTH)-treated fetal rat femur. As PTH significantly reduced the calcium and phosphorus contents of the femora, probably by stimulating bone resorption, KCA-098 seems to inhibit bone resorption. In fact, KCA-098 inhibited the PTH-induced release of ⁴⁵Ca from pre-labeled fetal rat femora into the medium in organ culture. Coumestrol also inhibited the release of ⁴⁵Ca from bone into the medium. However, KCA-098 did not increase the uterine weight of ovariectomized rats, whereas coumestrol did so. Thus KCA-098 is a unique, new inhibitor of bone resorption that has no estrogenic activity.