雌激素治疗骨质疏松大鼠正畸牙移动的实验

目的 探讨雌激素对骨质疏松患者正畸牙齿移动的影响及其对牙槽骨的作用。方法 选用３０只雌性ＳＤ大鼠随机分为３组,健康对照组、骨质疏松组、骨质疏松雌激素治疗组。测量３组不同时期牙齿移动的距离、破骨细胞计工进行组织学观察。结果 治疗１个月后,骨质疏松组较健康对照组正畸牙牙移动增加４３．３％,雌激素治疗组增加３０．７％;破骨细胞计数骨质疏松组较健康对照组增加６４．４％,雌激素治疗组增加３２．９％。治疗２个     

Effects of vascular endothelial growth factor on osteoclast induction during tooth movement in mice

For orthodontic tooth movement, remodeling of the alveolar bone is maintained by a repeated process of bone resorption and new bone formation, controlled, respectively, by osteoclasts and osteoblasts. Recently, we have found that recombinant human vascular endothelial growth factor (rhVEGF) acts as a macrophage colony-stimulating factor in osteoclast induction in osteopetrotic (op/op) mice. The purpose of this study was to investigate whether rhVEGF stimulates osteoclast differentiation during experimental tooth movement. Purified rhVEGF was injected once into the buccal gingival groove around the incisors. An experimental appliance with a helical loop was bonded onto the upper incisors, and an initial force of 1.0 g was applied for three days. The number of osteoclasts appearing in the periodontal ligament space on the pressure side of the alveolar bone was increased markedly. These results suggest that local administration of rhVEGF enhances the number of osteoclasts, and may increase the rate of orthodontic tooth movement. Abbreviations: recombinant human vascular endothelial growth factor (rhVEGF), macrophage colony-stimulating factor (M-CSF), osteopetrotic mice (op/op mice),fms-like tyrosine kinase (Flt-1), periodontal ligament (PDL), phosphate-buffered saline (PBS), tartrate-resistant acid phosphatase (TRAP), and analysis of variance (ANOVA).     

Inhibitory effects of IL-12 on experimental tooth movement and root resorption in mice

ObjectiveInterleukin (IL)-12 is an important cytokine for innate and adaptive immunity. We previously reported that IL-12 inhibits tumour necrosis factor (TNF)-α-mediated osteoclast formation by inducing apoptosis. We also reported that TNF-α plays an important role in mechanical loading-induced osteoclast formation and bone resorption during orthodontic tooth movement. In this study, we investigated the effects of IL-12 on mechanical tooth movement in mice.DesignA Ni–Ti closed coil spring was inserted between the upper incisors and the upper left first molar in mice. IL-12 was injected locally adjacent to the first molar every other day during the experimental period, at doses varying from 0 to 1.5 μg/day. After 12 days, the animals were killed and their jaws were processed for histological evaluation using tartrate-resistant acid phosphatase (TRAP) and TdT-mediated dUTP-biotin nick end-labelling (TUNEL) staining, and measurements of the root resorption area.ResultsIn the IL-12-treated mice, tooth movement and root resorption appeared to be reduced. In TUNEL-stained sections, many apoptotic cells were recognized on the pressure side in the IL-12-treated mice.ConclusionsOur findings suggest that IL-12 inhibits not only mechanical tooth movement, but also root resorption during orthodontic tooth movement. These findings may arise through apoptosis induced by IL-12.     

牙周加速成骨正畸临床应用效果的研究进展

牙周加速成骨正畸(PAOO)是指对牙槽骨进行骨皮质切开,并在切开骨表面进行颗粒骨移植以辅助正畸治疗。骨皮质切开诱导的局部加速现象可诱导破骨活性增加,加速骨代谢,从而有效加速正畸牙移动,缩短疗程,并可以减少牙根吸收等正畸并发症的发生。颗粒骨的植入能扩大正畸牙的移动范围,拓宽正畸治疗的适应证,保证牙周健康,提高治疗稳定性。本文就PAOO对正畸治疗中牙移动速率、骨增量效果以及牙根吸收的临床效果作一综述,以便为该技术的临床应用提供参考。     

Effect of diabetes on orthodontic tooth movement in a mouse model

Orthodontic tooth movement is achieved by the remodeling of alveolar bone in response to mechanical loading. Type 1 diabetes results in bone remodeling, suggesting that this disease might affect orthodontic tooth movement. The present study investigated the effects of the diabetic state on orthodontic tooth movement. An orthodontic appliance was placed in normoglycemic (NG), streptozotocin-induced diabetes (DB), and insulin-treated DB (IT) C57BL6/J mice. Histomorphometric analysis and quantitative PCR of periodontium were performed. The DB mice exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphate (TRAP) -positive osteoclasts than NG mice. This was associated with increased expression of factors involved in osteoclast activity and recruitment (Rankl, Csf1, Ccl2, Ccl5, and Tnfa) in DB mice. The expression of osteoblastic markers (Runx2, Ocn, Col1, and Alp) was decreased in DB mice. Reversal of the diabetic state by insulin treatment resulted in morphological findings similar to those of NG mice. These results suggest that the diabetic state up-regulates osteoclast migration and activity and down-regulates osteoblast differentiation, resulting in greater orthodontic tooth movement.     

Facilitation of experimental tooth movement by NOC-18, a long-acting nitric oxide donor

PurposeIn orthodontic tooth movement, osteoclasts play a crucial role in bone resorption on the compression side of the alveolar bone. It has been reported that nitric oxide is involved in bone remodeling caused by mechanical loading, and we previously reported that NOC-18, a long-acting nitric oxide donor, augmented RANKL-induced osteoclast differentiation in mouse monocytic RAW264 cells as well as mouse bone marrow macrophages. In this study, we investigated whether NOC-18 facilitated experimental tooth movement in mice.Materials and methodsEight-week-old male ddY mice were used. Experimental tooth movement was induced by the insertion of an orthodontic elastic between the left maxillary first molar and second molar. Just after the insertion of the elastic, NOC-18 was intraperitoneally administered once, and mice were killed after 3 days. For the detection of osteoclasts, HE staining, TRAP staining, and immunostaining for cathepsin K were performed.ResultsAn intraperitoneal injection of NOC-18 significantly increased the distance of experimental tooth movement. Furthermore, the number and area of osteoclasts on the compression side of the alveolar bone surface was significantly higher in the NOC-18 group.ConclusionThese results suggested that systemic administration of NOC-18 might have some effect to facilitate experimental tooth movement in mice via the augmentation of osteoclast differentiation on the compression side of the alveolar bone.     

The role of tumor necrosis factor receptor type 1 in orthodontic tooth movement

Orthodontic tooth movement is dependent on osteoclast activity. Tumor necrosis factor (TNF)-alpha plays an important role, directly or via chemokine release, in osteoclast recruitment and activation. This study aimed to investigate whether the TNF receptor type 1 (p55) influences these events and, consequently, orthodontic tooth movement. An orthodontic appliance was placed in wild-type mice (WT) and p55-deficient mice (p55(-/-)). Levels of TNF-alpha and 2 chemokines (MCP-1/CCL2, RANTES/CCL5) were evaluated in periodontal tissues. A significant increase in CCL2 and TNF-alpha was observed in both groups after 12 hrs of mechanical loading. However, CCL5 levels remained unchanged in p55(-/-) mice at this time-point. The number of TRAP-positive osteoclasts in p55(-/-) mice was significantly lower than that in WT mice. Also, there was a significantly smaller rate of tooth movement in p55(-/-) mice. Analysis of our data suggests that the TNFR-1 plays a significant role in orthodontic tooth movement that might be associated with changes in CCL5 levels.     

Influences of ovariectomy on experimental tooth movement in the rat

Estrogen withdrawal, which is important in the pathogenesis of post-menopausal osteoporosis, accelerates bone metabolism with a negative calcium balance. Therefore, it is hypothesized that estrogen deficiency could affect the rate of experimental tooth movement and alveolar bone remodeling. Six-week-old rats received a bilateral ovariectomy (OVX) or sham operation. Fourteen days later, rats were subjected to lateral tooth movement in the upper molar with nickel-titanium wire of 10 g of force. OVX significantly increased the rate of experimental tooth movement from 12 days after experimental tooth movement (p < 0.001). Eighteen days after the start of tooth movement, bone histomorphometry demonstrated that OVX significantly elevated the osteoblast surface, osteoclast surface, and number of osteoclasts (p < 0.05) in the alveolar bone. These findings indicated that estrogen deficiency caused significantly rapid orthodontic tooth movement, and that the acceleration of tooth movement could be due to the further activation of alveolar bone turnover.     

持续力和间歇力对牙移动骨改建的影响

正畸矫治力的作用时间对牙移动和牙槽骨改建的速度有直接影响,国内外许多学者对此进行了研究。该文就持续力和间歇力对牙移动速度、牙周膜牙槽骨改建和牙体应力反应的影响作一简要综述。选择合适的正畸加力方式,有助于临床医师有效控制牙移动,缩短正畸疗程。     

The effect of osteoporosis on periodontal status, alveolar bone and orthodontic tooth movement. A literature review

Osteoporosis, an age-related condition, is defined as a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration with a consequent increase in bone fragility and susceptibility to fracture. It is considered the most common bone metabolic disease and it constitutes a major public health problem. Several studies indicate that osteoporosis may be related to decreased oral bone density and alveolar bone loss. In osteoporotic patients, uncoupling of bone resorption and bone formation has taken place. Both bone resorption and bone formation are accelerated, and excessive bone resorption usually leads to loss of attachment. Osteoporosis could also affect the rate of tooth movement through the involvement of alveolar bone. In healthy individuals, bone is constantly being remodeled in the coupled sequence of bone resorption and formation. When a force is applied to a tooth, alveolar bone formation and resorption occur predominantly on the tension and pressure sides of the root, respectively, and the tooth moves with increased alveolar bone remodeling. Experimental studies suggest that systemic-osteoporotic hormone imbalance increases bone turnover and accelerates tooth movement while under orthodontic treatment. Based on these observations it can be concluded that deviations in bone turnover and consequent periodontal problems influence the response to orthodontic forces, and this should be taken into consideration when planning orthodontic treatment in adult patients with metabolic bone disease, especially postmenopausal females or those on chronic medication affecting bone metabolism.     

Immunohistochemical localization of alphavbeta3 integrin receptor during experimental tooth movement.

During orthodontic treatment, multinucleated clast cells carry out the resorption of mineralized tissues. Adhesion of clast cells to the mineralized tissues is mediated by transmembrane cell-surface glycoproteins called integrins, specifically by the alphavbeta3 integrin, which plays an important role in the process of bone resorption. The role of the alphavbeta3 integrin in bone resorption leading to osteoporosis has been demonstrated, but its role in alveolar bone and root resorption during orthodontic tooth movement is unknown. This study examined the expression of the alphavbeta3 integrin during experimental tooth movement. Tooth movement was achieved in 16 male Sprague-Dawley rats (each weighing 120-200 g) with elastic bands between their maxillary first and second molars. The molar-bearing segments were dissected and processed for histologic and immunohistochemical examination. The expression of alphavbeta3 integrin was examined with 2 primary antibodies: a polyclonal anti-alphav integrin subunit antibody and a polyclonal anti-beta3 integrin subunit antibody. Negative controls were similarly processed but without incubation with primary antibodies. The alphavbeta3 integrin was expressed both by osteoclasts associated with alveolar bone resorption and by odontoclasts associated with root resorption during experimental tooth movement. Furthermore, the beta3 integrin subunit was expressed by the epithelial rests of Malassez in the periodontal ligament. Negative controls did not show immunolabeling. The alphavbeta3 integrin adhesion receptor is expressed during experimental tooth movement and might be involved in the process of mineralized tissue resorption and the functions of the epithelial rests of Malassez.     

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。     

Later orthodontic appliance reactivation stimulates immediate appearance of osteoclasts and linear tooth movement

Background: Delays in the appearance of osteoclasts at compression sites occur after orthodontic appliance reactivation, when this is done during both the period of osteoclast recruitment and the peak expansion in the osteoclast population. This experiment examines osteoclasts and tooth movement in alveolar bone after appliance reactivation coinciding with alveolar bone formation and the time when reactivation osteoclasts first appear (ie, 10 days after initial appliance activation). Methods: Bilateral orthodontic appliances were activated to mesially tip maxillary molars with 40 cN in 144 rats. After 10 days, all rats were randomized into two groups of 72. Group I had appliances reactivated in precisely the same manner as the first activation. Group II had appliances sham-reactivated. Nine to 12 rats were then sacrificed at 1, 3, 5, 7, 10, and 14 days in both groups (eg, day 1 represents an interval of 11 days after the first appliance activation and 1 day after either sham or real reactivation). Orthodontic movement was measured cephalometrically; changes in osteoclasts and root resorption were assessed at both compression and tension sites histomorphometrically. Results: Teeth in the reactivated group (Group I) displayed linear tooth movement (62.6 μm/day), and 0.9 mm tooth movement by day 10. Significant increases in osteoclast numbers, osteoclast surface percentage, and surface per individual osteoclast were evident in these animals by 1 day postreactivation (P < .01). Significant treatment-related increases in root resorption were not evident at compression sites at any time. Conclusions: These findings indicate that, after appliance reactivation during the time when reactivation osteoclasts appear, a second cohort of osteoclasts can be recruited immediately, along with immediate and substantial tooth movement and no greater risk of root resorption. (Am J Orthod Dentofacial Orthop 1998;114:692-7)     

Effect of appliance reactivation after decay of initial activation on osteoclasts, tooth movement, and root resorption

Clinical orthodontists frequently reactivate appliances following decay. Studies of tooth movement and tissue responses following reactivations indicate that linear tooth movement and rapid recruitment of osteoclasts can be achieved if reactivation is timed to coincide with the latter part of the bone remodeling cycle initiated by the first activation. Both can be delayed if reactivations are timed for the early part of the previous cycle. The objective of this study was to examine tooth movement, root resorption, and osteoclast recruitment following appliance reactivation after the first activation had decayed. Bilateral orthodontic appliances were activated with 40 cN in 144 rats to mesially tip the maxillary molars. After 16 days, rats were randomized into two groups of 72. In group 1, appliances were reactivated in precisely the same manner as the first activation. In group 2, appliances were sham-reactivated. Rats were sacrificed at 1, 3, 5, 7, 10, and 14 days. Orthodontic movement was measured cephalometrically; changes in osteoclasts and root resorption were assessed at both compression and tension sites histomorphometrically; tartrate-resistant acid phosphatase (TRAP) was measured in alveolar bone and serum biochemically. Orthodontic tooth movement was linear in group 1, but osteoclasts required 3 to 5 days to appear. There were no group- or time-related differences in root resorption. Bone TRAP levels were elevated in both groups but dropped significantly (p<0.01) in group 2 at day 7. Appliance reactivations that followed decay of the first activation produced efficient tooth movement without increased risk of root resorption, but these changes were not accompanied by rapid osteoclast recruitment at compression sites. Timing appliance reactivations for the latter portion of the previous bone remodeling cycle could have significant clinical advantages because the delay period seen in tooth movement following a single activation or short-term reactivation can be avoided.     

Intermittent force in orthodontic tooth movement

A single orthodontic activation lasting one hour can initiate tooth movement. The purpose of this study is to examine tooth movement, osteoclasts, and root resorption in rats following several one-hour activations. Rats (n = 144) were randomly assigned to intermittent (multiple activations of 1 hr/day), continuous, and sham appliances. Twelve rats were killed at 3, 5, 7, and 14 days. Tooth movement, osteoclasts, osteoclast %, and root resorption % were quantified. Continuous force moved molars mesially at days 3 and 14 (p < 0.05), but intermittent and sham did not. Intermittent and continuous force increased osteoclast numbers at days 3, 5, and 7 (p < 0.05). Continuous force increased osteoclast surface on days 3 and 14 (p < 0.05). Continuous force increased root resorption at days 5, 7, and 14 (p < 0.05). These results demonstrate that orthodontic force for one hour in 24 stimulates osteoclasts at compression sites but does not stimulate tooth movement or root resorption.     

正畸牙移动中骨吸收机制及其调控的研究进展

破骨细胞在正畸牙移动压力侧骨吸收过程中发挥着重要的作用,针对破骨细胞分化成熟及其发挥功能的调控研究,能为正畸治疗中控制牙齿移动提供新的思路,同时有助于防治正畸治疗中出现的牙根外吸收等。     

The Effect of Leptin on Rat Maxillary Alveolar Bone under Mechanical Stimuli

Mechanical stress is known to play an important role in bone remodeling and homeostasis, by influencing processes of bone formation and bone resorption. Some hormones have been shown to influence not only bone homeostasis but also mechanical stress-induced bone remodeling. For example, leptin, a hormone secreted by adipocytes that controls mammal's appetite, has been suggested to regulate bone volume. Here, we have investigated the effects of leptin on the remodeling of alveolar bone induced by experimental tooth movement in leptin receptor-defective Wistar fatty rats. Seven days after applying tractive force on a right maxillary first molar, a larger tooth displacement was observed in heterozygous (fa/+) compared to wild-type (+/+) animals. Histomorphometry demonstrated a significantly elevated osteoclast number in the alveolar bone of heterozygous (fa/+) (p<0.05) when compared to that in wild-type (+/+) rats, indicating that leptin receptor deficiency enabled rapid orthodontic tooth movement by accelerated bone resorption. Our findings suggested that leptin could influence mechanical stress-induced bone remodeling.     

雷洛昔芬对牙周炎合并系统性绝经后骨质疏松症小鼠模型局部牙槽骨破坏的影响

目的：探讨雷洛昔芬对牙周炎合并系统性绝经后骨质疏松症（PMO）小鼠模型局部牙槽骨破坏的影响。方法：无特定病原级雌性成熟Wistar小鼠,适应性喂养7 d 后,随机分为空白组（保留两侧卵巢,只切除卵巢组织周围与卵巢重量相当的脂肪组织）、对照组（切除两侧卵巢+口腔正畸结扎丝结扎）、实验组（切除两侧卵巢+口腔正畸结扎丝结扎+雷洛昔芬试剂）,每组各15只。术后4周拍摄CT,检测骨密度和骨吸收情况,体视显微镜观察牙槽骨破坏情况,酶联免疫吸附测定法（ELISA）检测破骨相关因子白细胞介素1(IL-1)、IL-1α、转化生长因子(TGF)、肿瘤坏死因子α(TNF-α)、TNF-β的表达水平。采用SPSS 18.0软件包对数据进行统计学分析。结果：对照组新骨形成少于实验组。亚甲蓝染色结果显示,对照组小鼠骨显著吸收,体视显微镜下可见骨破坏,实验组小鼠骨吸收程度较轻。与空白组相比,对照组、实验组牙槽骨密度降低而牙槽骨丧失、IL-1、IL-1α、TGF、TNF-α、TNF-β显著升高（P<0.05）;对照组牙槽骨密度显著低于实验组（P<0.05）,牙槽骨丧失、IL-1、IL-1α、TGF、TNF-α、TNF-β显著高于实验组（P<0.05）。结论：雷洛昔芬可减少PMO牙周炎症小鼠牙槽骨吸收、破骨细胞因子表达,防止牙槽骨破坏而有效防止牙周炎进展。     

Raloxifene reduces the risk of local alveolar bone destruction in a mouse model of periodontitis combined with systemic postmenopausal osteoporosis

OBJECTIVEPeriodontitis is characterized by local inflammation leading to tooth loss and severe destruction of alveolar bone. Raloxifene is a selective estrogen receptor modulator (SERM) that halts estrogen deficiency-induced systemic bone loss in postmenopausal osteoporosis without the side effects of cancer in breast and uterus. In this study, we examined the effects of raloxifene on alveolar bone mass in a mouse model with estrogen deficiency-induced periodontitis.METHODSPeriodontitis was induced by the injection of lipopolysaccharide (LPS) into the lower gingiva in ovariectomized (OVX) mice, and the alveolar bone and femur bone mineral density (BMD) were analyzed by dual-energy X-ray absorptiometry. To explore the direct osteoclast inhibitory effect of raloxifene, a co-culture system for osteoclast formation and organ culture of alveolar bone was established.RESULTSWhen OVX mice were treated with raloxifene, the bone loss in both alveolar bone and femur were abrogated. Interleukin 1 and/or LPS stimulated the osteoclast formation and bone-resorbing activity; however, raloxifene did not show any inhibitory effect on the osteoclast formation or function. In vivo local injection of raloxifene also did not prevent bone resorption in a mouse model of periodontitis. However, the systemic treatment of raloxifene using a mini-osmotic pump did prevent the loss of BMD of alveolar bone induced by LPS.CONCLUSIONThese results suggest that the SERM raloxifene systemically maintain alveolar bone mass in a mouse model of periodontitis with osteoporosis. Increasing the alveolar bone mass by SERMs treatment in patients with postmenopausal osteoporosis may be a useful approach to preventing the destruction of alveolar bone in late-onset periodontitis.