功能矫治大鼠前伸下颌后血中 PGE2的节律变化

目的：观察戴用功能矫治器对大鼠血液中的 PGE2昼夜节律的影响。方法：选择4周龄健康 Wistar 雄性大鼠54只,随机等量分为白天组、全天组、对照组（n ＝18）。戴自制导板下颌前伸的功能矫治器。大鼠戴用矫治器1周后,在相应时间点处死大鼠（n ＝3）,对其血液样本中 PGE2含量进行测定,并对数据用单余弦拟合法做拟合度检验。结果：对照组数据检验假设成立,P ＜0．05,2个实验组数据检验假设不成立,P ＞0．05。结论：大鼠血中 PGE2水平呈现昼夜节律性,功能矫治使大鼠血中PGE2昼夜节律消失。     

The effects of elevated fibroblast growth factor 23 on mandibular growth in rats

ObjectiveThe aim of this study is to elucidate the local effects of fibroblast growth factor 23 (FGF23) in on mandibular condylar growth in growing rats.DesignGrowing Sprague–Dawley rats received intra-temporomandibular joint injections of phosphate buffer solution (PBS), adenovirus-mediated green fluorescent protein (Ad-GFP) or adenovirus-mediated fibroblast growth factor 23 (Ad-FGF23), which were marked as groups A, B, and C, respectively. In vitro, we treated rat mandibular cartilage chondrocytes with PBS, Ad-GFP, and Ad-FGF23.ResultsThe mandibular condyles in group C grew smaller sizes than those in the other control groups due to significant differences among the experimental and control groups with the value of C–D, Q–R (P ≤ 0.05), accompanied by diminished bone mass of sub-cartilage condyles via micro CT analysis. Histologically, the length of the hypertrophic zone was diminished and was associated with decreasing chondrocyte proliferation in group C. Quantitative real-time PCR indicated significant decreases in the expression of chondrogenesis marker genes, including Type X collagen (Col X) and SRY-type box 9 (Sox 9). Moreover, elevated Ad-FGF23 suppressed chondrocyte proliferation and the expression of the chondrogenic differentiation markers Col X and Sox 9 of in vitro.ConclusionsLocal injection of FGF23 suppressed the development and decreased the bone mass of condyles through the decreasing the formation of condylar cartilage, specifically by regulating condylar cartilage cell viability and chondrogenesis expression.     

Propulsive appliance stimulates the synthesis of insulin-like growth factors I and II in the mandibular condylar cartilage of young rats

Functional orthopedic appliances correct dental malocclusion partially by exerting indirect mechanical stimulus on the condylar cartilage, modulating growth and the adaptation of orofacial structures. However, the exact nature of the biological responses to this therapy is not well understood. Insulin-like growth factors I and II (IGF-I and IGF-II) are important local factors during growth and differentiation of several tissues, including cartilage. The aim of this study was to verify the mRNA and protein expression of IGF-I and IGF-II in the condylar cartilage of young male Wistar rats that used a mandibular propulsive appliance for 3, 5, 7, 9, 11, 13 or 15 days. For this purpose, sagittal sections of decalcified and paraffin-embedded condyles were submitted to immunohistochemistry and in situ hybridization. IGF-I and IGF-II expression increased with developmental age in the control and treated rats. After 9 days of treatment the positivity for both peptides in the animals that wore the propulsive appliance increased even more, expressively different from the age-matched controls. The expression patterns of both IGFs were similar, although IGF-I labelling was stronger. Furthermore, the enhanced expression of both peptides was in parallel with the proliferating cell nuclear antigen (PCNA) positivity, a proliferation cell marker. The modulation of IGF-I and IGF-II expression in the condylar cartilage in response to the propulsive appliance suggests that both peptides are involved in the mandibular adaptation during this therapy.     

Effects of growth hormone and ultrasound on mandibular growth in rats: MicroCT and toxicity analyses

It has been shown by previous studies that mandibular growth can be enhanced by the systemic administration of recombinant growth hormone (rGH) and/or local application of therapeutic low intensity pulsed ultrasound (LIPUS). The purpose of this study was to determine if local injection of rGH and application of LIPUS to the temporomandibular joint (TMJ) would synergistically enhance mandibular growth. In an animal study, the effect of rGH, LIPUS, and combination of rGH and LIPUS on male Sprague–Dawley rats was observed. Mandibular growth was evaluated by measuring total hemimandibular and condylar bone volume and bone surface area as well as condylar bone mineral density (BMD) after 21 days on dissected rats’ mandibles using micro-computed tomography (MicroCT). The expression of c-jun mRNA extracted from the liver of each of these rats was also quantified by real-time polymerase chain reaction to evaluate possible systemic effect of local rGH administration. Significant growth stimulation was observed in the mandibular and condylar bone of the animals treated with rGH, LIPUS, and rGH/LIPUS combined when compared with the control group. Bone volume, surface area, condylar bone mineral density, and c-jun expression were also compared between the treatment groups and the control in the liver. The results suggest that mandibular growth may be enhanced by injection of rGH or LIPUS application. The current study although showed synergetic effect of rGH and LIPUS application in increasing mandibular condylar head length, there was no significant changes in mandibular bone volume using both treatments together when compared to the two individual treatments. Moreover, combined rGH and LIPUS decreased condylar bone mineral density than each treatment separately. Future research could be directed to investigate the effects of different rGH doses and/or different LIPUS exposures parameters on lower jaw growth.     

下颌前伸对成年大鼠髁突软骨Ⅹ型胶原表达的影响

目的:建立年轻成年大鼠下颌前伸动物模型,以X型胶原为检测指标,观察髁突软骨内成骨及其与下颌前伸持续时间的关系.方法: 9 周龄雌性大鼠75 只,分为3 组,其中2 组为实验组,另一组为对照组,实验组动物戴用统一规格自制的咬合前导矫治器,分别戴用12 h和24 h.3 组动物分别在实验后3、7、14、21、30 d处死后取双侧髁突组织,使用免疫组化和原位杂交方法从蛋白水平和基因水平检测髁突软骨组织切片中X型胶原的表达情况.结果:免疫组化结果显示, 24 h实验组X型胶原表达量在21 d时最高,且高于其他实验组;而12 h实验组峰值出现在30 d.原位杂交结果与免疫组化结果基本吻合.结论:功能矫治下颌前伸均能诱导年轻成年大鼠髁突软骨发生改建,但与12 h间歇性加力方式相比,24 h持续加力方式作用效果明显,且见效快.     

Effects of growth hormone and functional appliance on mandibular growth in an adolescent rat model

Objectives:To investigate the individual and synergistic effects of growth hormone (GH) and functional appliance (FA) on mandibular growth in an adolescent rat model.Materials and Methods:Forty adolescent (6-week-old) female Wistar rats were randomly divided into four groups (10 rats in each group). The control group received a sham treatment (intra-abdominal injection of phosphate-buffered saline), the GH group received an intra-abdominal injection of recombinant human growth hormone, the FA group was treated with a mandibular advancement device, and the GH+FA group received both the GH and FA treatments. The amount of mandibular growth in each group was measured quantitatively using cone-bean computed tomography. The growth of condylar cartilage and expression of matrix metalloproteinases–1 and –13 (MMP-1 and MMP-13) and type II and X collagen (Col II and Col X) were assessed using histological staining and immunostaining techniques.Results:After 4 weeks, there was significant mandibular growth in the FA group compared with the control group (P < .05). The GH+FA group had significantly greater mandibular length, thickness of condylar cartilage, and expression of MMP-1, MMP-13, Col II, and Col X in the cartilage than the other groups (P < .05). The GH+FA group and GH group had significantly greater weight than the FA and control groups (P < .05).Conclusions:The FA as well as GH+FA stimulated mandibular growth in adolescent rats.     

Forsus矫治器治疗发育高峰后期下颌后缩的疗效评价

目的:评价Forsus矫治器治疗生长发育高峰后期下颌后缩患者的临床效果、颅面软硬组织的改变。方法:应用Forsus矫治器对15例生长发育高峰后期的安氏Ⅱ类下颌后缩畸形患者进行矫治,进行上、下颌尖牙及磨牙间宽度测量,填写问卷调查表和治疗前、后的头影测量侧位片分析。采用SPSS10.0软件包对所得数据进行配对t检验。结果:SNB增加1.42°,ANB角减小1.65°,面突角减小2.12°,颏唇沟深度减小2.27mm,覆盖减小4.98mm,磨牙关系改善3.78mm。上切牙内收,下切牙唇倾;牙弓宽度增大。基本无异物感,不影响口腔功能。结论:Forsus矫治器能够有效促进下颌生长、改善磨牙远中关系及Ⅱ类软组织面型,适用于生长发育高峰后期患者的治疗。     

Interplay of mechanical loading and growth factors in the mandibular condyle

The mandibular condyle is an important growth site in the developing mandible. The growth of the condyle is known to be highly adaptable to functional factors. This property is exploited in orthodontics for the treatment of class II malocclusions and mandibular asymmetries. However, there is an ongoing debate on the efficacy of functional appliances. The comparison of experimental studies is complicated by the lack of detailed analyses of the load distribution within the condyle. In spite of this, there is a large body of evidence showing that mechanical manipulation of the condyle induces metabolic changes, and changes in the expression of growth factors and other signalling molecules. This review aims to give an overview of the role of growth factors in the condyle with special emphasis on their responsiveness to mechanical perturbation.     

功能矫治前伸下颌后大鼠髁突软骨雌激素受体变化规律的研究

目的了解雌激素受体（ｅｓｔｒｏｇｅｎｒｅｃｅｐｔｏｒ，ＥＲ）与髁突软骨增生、分化及适应性生长改建的关系，探讨功能矫形治疗的机理。方法选用５０只４周龄的雌性ＳＤ大鼠，分为实验组和对照组。实验组大鼠配戴自制功能性矫治器引导下颌前伸，应用葡聚糖活性炭吸附法（ＤＣＣ法）对髁突软骨中ＥＲ进行了检测和分析。结果大鼠髁突软骨中存在雌激素受体，且髁突软骨增生旺盛期时受体含量较高，而分化期时含量较低；功能矫形前伸下颌后，髁突软骨中ＥＲ含量明显增加。结论雌激素受体与髁突软骨的增生、分化及功能矫形后的适应性生长改建关系密切。本项研究证实了髁突软骨中存在雌激素受体的作用机制并进一步阐明了功能矫形治疗的机理。     

The influence of masseter activity on rat mandibular growth

Many studies have shown that mandibular and condylar growth is affected by compressive forces on mandibular bone and the condyle. It has been reported that chondroblastic differentiation and proliferation in chondrocytes play important roles in condylar growth. However, the influence of reduced compressive force on chondroblastic proliferation and mandibular bone formation is not fully understood. Thirty-six 3-week-old male Wistar rats were used in this study. In the experimental group, the masseter muscles were bilaterally resected to evaluate the influence of masticatory force on mandibular and condylar bone morphology. Six weeks after the operation, while the rats were in the pubertal growth stage, lateral X-rays were taken to analyze the skeletal pattern of the mandible. The form of the condyle and the thickness of the chondroblastic layers were evaluated by toluidine blue staining. Chondroblastic proliferation was identified by insulin-like growth factor-1 receptor (IGF-1r) immunostaining and bone resorption of the condyle was assessed by measuring tartrate-resistant acid phosphatase (TRAP) activity. Lateral X-rays of the mandible showed that rats in the experimental group tended to have large mandibular plane angles. The chondroblastic layer in the condyles of the experimental group rats was thinner than in the control group. The expression of IGF-1r immunopositive cells in the experimental group was significantly lower than in the control chondrocytes, and the number of TRAP-positive cells was significantly higher in the condylar bone of the experimental group. We conclude that masseter muscle activity is closely related to mandibular morphology during growth.     

Evaluation of effects of activator treatment on mandibular growth by analyzing components of condylar growth and mandibular rotation

PurposeThe objective of this study is to clarify the effects of activator treatment on mandibular growth in relation to condylar growth and total rotation of the mandible, and to investigate the relationships between the treatment responses and pretreatment facial morphology.Materials and methodsThirty Japanese girls with Class II division 1 malocclusion treated with activator were examined. Mean age at the start of treatment was 9.6 ± 1.6 years. Mean treatment duration was 19 ± 4 months. Lateral cephalograms obtained before and after treatment were used to analyze skeletal changes during treatment. Regional superimposition analysis was performed to evaluate activator effects by decomposing the mandibular growth into condylar growth and mandibular total rotation.ResultsThe changes in intermaxillary relationships were significantly correlated with vertical condylar growth and mandibular total rotation (P < 0.05 and P < 0.01). The changes in the forward displacement of the mandible were significantly correlated with sagittal condylar growth and mandibular total rotation (P < 0.05 and P < 0.01). Vertical condylar growth and mandibular total rotation were significantly correlated with pretreatment mandibular morphology (P < 0.05 and P < 0.01).ConclusionBoth the sagittal condylar growth and counterclockwise mandibular total rotation attributed to activator treatment contribute to forward displacement of the mandible. The activator effects are expected greater in patients with flat mandibular plane, small gonial angle, backwardly inclined mandibular ramus and long posterior facial height.     

正畸辅助儿童髁突囊内骨折外脱位伴下颌后缩的闭合性治疗

目的 ：尝试正畸辅助闭合性治疗儿童髁突囊内骨折外脱位伴颏部骨折及下颌后缩,并观察其短期治疗效果。方法 ：1例9岁儿童外伤后15 d就诊,临床及影像学检查诊断为颏部骨折,双侧髁突囊内骨折外脱位,伴下牙弓增宽、下颌后缩。取模设计模型外科,制作Herbst矫治器。全麻下手法复位双侧髁突并缩窄下牙弓,同时戴入矫治器前移下颌。结果 ：配戴1个月后去除矫治器,随访6个月后患者咬合关系正常,下颌运动无碍,锥形束CT（CBCT）显示双侧髁突愈合改建良好,颏部骨折对位愈合。结论 ：借助Herbst矫治器的辅助,可闭合性治疗儿童髁突骨折外脱位伴颏部骨折及下颌后缩,短期随访获得了良好的咬合关系、髁突形态及下颌功能。     

下颌螺旋扩弓器的改良与临床应用

目的 介绍改良下颌螺旋扩弓器的制作及临床应用.方法 将下颌传统固定式螺旋扩弓器进行了改良,并使用这种改良式下颌扩弓器对89例患者进行上下颌联合扩弓正畸治疗,其中安氏Ⅰ类42例,安氏Ⅱ例37例,安氏Ⅲ类10例.错(牙合)问题有:牙齿拥挤、深覆(牙合)、反(牙合)、深覆盖、牙弓前突等.并对89例患者的下颌牙弓的宽度进行了测量分析.结果 89例正畸患者下颌尖牙、前磨牙、磨牙宽度均明显增宽,变化均有统计学意义.第二双尖牙间的宽度增加最大,平均6.14±2.56mm.结论 这种改良式下颌扩弓器将其所释放的力量同时施在下颌后牙和牙槽骨上,以期让后牙和牙槽骨都产生颊向移动,扩弓效果更为明显和稳定.     

Current concepts on functional appliances and mandibular growth stimulation

The mode of action of functional appliances, particularly in relation to stimulating mandibular growth, is a controversial subject. Many of the reports concerning growth effects of functional appliances have been characterized by poor methodology. In assessing functional appliances, results from prospective randomized clinical trials should be given prominence. On the basis of available evidence, it cannot be concluded that functional appliances are effective in stimulating and increasing mandibular growth in the long term. Although favourable growth changes have been reported following phase 1 therapy, they are generally not substantial and long term stability appears to be poor.     

下颌前伸对大鼠髁突软骨VEGF表达影响的研究

目的：探讨引导大鼠下颌前伸后,髁突软骨中血管内皮细胞生长因子（VEGF）表达水平的变化。方法：50只35d龄雌性SD大鼠随机分为5组,每组随机分为实验组（5只）和对照组（5只）;实验组大鼠24h佩戴自制功能性矫治器引导下颌前伸;实验后3d、7d、14d、21d和30d分别处死各组大鼠;免疫组化方法检测髁突软骨中VEGF的表达。结果：对照组髁突软骨VEGF表达随时间延长而减弱,后部区域VEGF表达强于前部和中部：实验后第14d,21d和30d实验组VEGF表达强于相应对照组（P〈0．05）,其中14d时软骨后部VEGF表达较对照组增强幅度最大。结论：下颌前伸后大鼠髁突软骨细胞VEGF表达增强,说明其参与了软骨内骨化过程。     

碱性成纤维细胞生长因子促进颌骨缺损修复的研究

目的 :评价碱性成纤维细胞生长因子 (bFGF)对成骨的促进作用 ,以期为颌骨缺损提供一种较为理想的替代材料。方法 :18只成年兔双侧下颌骨下缘各造成 15mm× 6mm的全层骨膜骨质缺损 ,每一缺损作为一个实验单位 ,按自身同期配对设计 ,分别植入复合骨和天然型无机骨 (NNB)。术后 3、6、12周取下标本 ,进行甲苯胺蓝染色观察、四环素荧光检查以及组织学成骨面积定量分析。结果 :复合骨新骨形成及钙化早 ,同期成骨面积大于NNB(P <0 .0 1)。结论 :合适的复合条件下bFGF可有效地促进软骨及骨的生长 ,复合骨新骨形成及钙化早 ,同期成骨量多 ,修复效果优于NNB。     

Diagnostic reliability of mandibular second molar maturation in the identification of the mandibular growth peak: A longitudinal study

Objective:To investigate the diagnostic reliability of mandibular second molar maturation in assessing the mandibular growth peak using a longitudinal design.Materials and Methods:From the files of the Burlington and Oregon growth studies, 40 subjects (20 from each collection, 20 males and 20 females) with at least seven annual lateral cephalograms taken from 9 to 16 years were included. Mandibular second molar maturation was assessed according to Demirjian et al., and mandibular growth was defined as annual increments of Co-Gn distance. A full diagnostic reliability analysis (including positive likelihood ratio) was performed to establish the diagnostic reliability of dental stages E, F, and (pooled) GH in identifying the imminent mandibular growth peak.Results:None of the dental maturation stages reliably identified the mandibular growth peak with greatest overall mean accuracy and positive likelihood ratio of 0.77 (stage F) and 2.7 (stage E), respectively.Conclusions:Use of the mandibular second molar maturation is not recommended for planning treatment requiring identification of the mandibular growth peak.     

Permanent reduction of mandibular size and bone stiffness induced in post-weaning rats by cyclophosphamide

It has been previously reported that several doses of cyclophosphamide (CPA) reduce body weight gain, diaphyseal torsional strength and longitudinal femoral growth in the growing rat. The present study was thus designed to estimate both the initial and the possible long-term effects of CPA treatment, by analyzing mandibular dimensions and biomechanical performance of the bone in adulthood in rats treated with the drug around weaning. Female Sprague-Dawley rats (N = 20), 26 d of age, received 100 mg/kg of CPA by the intraperitoneal route during days 0, 7 and 21 of the experimental period. Controls (C) received saline. Groups of rats were sacrificed at day 28 to estimate initial changes induced by the drug and on day 126 in order to determine long-term effects. The dimensions of the excised mandibles were measured directly between anatomical points; the geometry and material biomechanical quality of mandibular bone were assessed using a three-point bending mechanical test in an Instron Universal Testing Machine model 4442. CPA reduced body weight, body length and mandibular size (posterior part of the bone) significantly, when the parameters were measured at day 28. They did not recover with time, which means that catch-up growth did not occur and that the overall growth of the body was permanently affected by the drug. CPA treatment was also associated with a marked depression of the natural increase in the mandibular bone mass (cross-sectional area). The bending cross-sectional moment of inertia of the fracture sections (xCSMI) was also negatively affected by treatment. Significant decreases of both ultimate load and stiffness were also observed. The above structural parameters did not recover enough with time to attain control values at the end of the study. The intrinsic stiffness (E) of the mandibular bone was not affected by treatment. These findings suggest that CPA treatment during early postnatal life causes permanent changes in mandibular morphology and affects the adaptation of mandibular bone architecture to body growth, thus not allowing complete compensation at the end of the study because of an inadequate distribution of the resistive material through its cross-section rather than a qualitative impairment of cortical bone.     

Prediction of mandibular growth in children with anterior crossbite

The purpose of this study was to propose mathematical models for predicting mandibular growth direction and amount in children with anterior crossbite from 4 to 9 years of age using lateral cephalograms. Lateral cephalograms of 25 Japanese children with anterior crossbite at 4 years (T1) and 9 years (T2) were traced and measured. The measurements were performed on 18 angular and 13 linear measurements. Variation of the angle NSGn and the distance S-Gn were used to represent the variation of growth direction and amount, respectively. The data were analyzed statistically by multiple regression analysis. The analysis revealed 2 models for the prediction of the mandibular growth. The variation of the direction of mandibular growth can be predicted by 68% with the regression equation using the angles NSAr, Nasal floor to SN and SNA at T1. The variation of the amount of mandibular growth can be predicted by 69% with the regression equation using the distance Ar-Me, the angles Nasal floor to SN, NSBa and Interincisal angle at T1. The parameters for the mandibular growth prediction for crossbite children are different from those of children with normal occlusion. This study will be of great importance to predict future mandibular growth of children with anterior crossbite.     

The effect of rheumatoid arthritis and functional loading on the structure of the mandibular condyle in a transgenic mouse model: An FTIR study

ObjectiveThe objective of the present study was to investigate the effect of rheumatoid arthritis and functional loading through diet modification on the biochemical properties of the mandibular condyle in a transgenic mouse model and compare with healthy littermates.DesignTwenty three, 4-week old hybrid male mice were used. Eleven were of transgenic line hTNF 197 (Tg 197 – with rheumatoid arthritis – RA) and 12 healthy littermates, both from mixed background CBAxC57BL/6. Four groups of mice were formed. Group 1 [n = 5, RA-hard] included transgenic mice and received ordinary (hard) diet; group 2 [n = 6, RA-soft] included transgenic line and received soft diet; group 3 [n = 6, control-hard] were healthy littermates receiving ordinary (hard) diet and group 4 [n = 6, control-soft] were healthy littermates with soft diet. Experimental period was 28 days. Following sacrifice, the mandibular condyles were subjected to micro-attenuated reflection Fourier transform infrared spectroscopy (micro-ATR FTIR) to reveal collagen/proteoglycan conformation of the condylar cartilage, while resin-embedded and metallographically polished specimens were evaluated through reflection FTIR microscopy to identify mineralization status of the corresponding condylar bone.ResultsThe multivariable analysis revealed significantly lower a-helix to amide I percentage area ratio for the transgenic animals after adjusting for diet (β = −4.29, 95% CIs: −8.52, −0.06; p = 0.04). Mineral phase indices did not differ significantly between RA and control groups regardless the type of diet.ConclusionsInternal derangement of the anatomical structure with denaturation in the collagen structural components of the mandibular condyles of the RA animals was found, while no association with functional loading through diet modification was recorded.