Changes in condylar cartilage after anterior mandibular displacement in juvenile pigs

Adaptive remodelling of the mandibular condyle in response to mandibular advancement is the mechanism exploited by orthodontic forward displacement devices.ObjectiveThis work investigated the expression of collagens, matrix metalloproteinases and vascular endothelial growth factor during this process.DesignTwenty juvenile pigs were randomly divided into two experimental groups, where the treatment group was fitted with mandibular advancement splints, and the control group was not. Changes in the mRNA content of condylar cartilage tissue was then were measured by real-time PCR using specific primers after 4 weeks of treatment.ResultsThe temporal pattern of the expression of Col1 and MMP13 during condylar adaptation coincided with that during natural condylar growth. The amount of the expression of Col10 during condylar adaptation was significantly lower (p < 0.05), whereas the expression of Col2, MMP8 and VEGF was significantly higher compared to natural growth (p < 0.05).ConclusionsIt is suggested that condylar adaptation in growing pigs triggered by mandibular forward positioning results not only from passive adaptation of cartilage, but also involves growth affected processes. Our results showed that mechanical strain produced by mandibular advancement induced remodelling and revascularization in the posteriocranial mandibular condyle. These results are mostly consistent with former published histological and histomorphometrical analyses.     

导下颌向前对生长期大鼠髁突软骨结缔组织生长因子表达的影响

目的:通过建立导下颌向前的Sprague-Dawley (SD)大鼠的动物模型进行免疫组化实验,观察结缔组织生长因子(CTGF)在髁突软骨中分布的变化,探讨CTGF对前伸下颌后的髁突软骨的影响。方法:建立SD大鼠动物模型,选取45只5周龄SD 雌性大鼠,体重约100 g,随机分为对照组(20只)和实验组(25)只,组内再随机平均分为5组(3、7、14、21 和30 d)。实验组动物24 h佩戴改良可摘式上颌斜面导板矫治器,对照组动物不做处理。免疫组化染色标记CTGF,观察髁突软骨各层CTGF的表达变化。对CTGF的阳性表达量进行半定量分析。结果:对照组和实验组中髁突软骨组织中均有CTGF的表达,主要分布于肥大层和增殖层。实验组不同时间点髁突肥大层和增殖层中CTGF的平均光密度值分别高于对照组的平均光密度值(P<0.05 ) 。与对照组相比,实验组7 d后髁突肥大层和增殖层中CTGF的表达开始上升,到第14天达到最高,之后CTGF表达回落,但仍高于对照组(P<0.05 )。实验3 d、30 d,肥大层和增殖层中CTGF实验组与对照组相比无统计学差异。结论:CTGF可能参与了功能负荷改变所导致的髁突软骨适应性改建活动。     

富血小板血浆修复生长期兔髁突软骨损伤后下颌骨生长发育的三维评估研究

目的　建立生长期髁突软骨及软骨下骨损伤动物模型,利用Materialise Proplan CMF 3.0软件对下颌骨进行三维测量,探讨富血小板血浆（PRP）对生长期髁突软骨损伤修复及维持下颌骨生长发育的作用。方法　生长期新西兰大白兔30只随机分为3组。PRP修复组（10只）建立髁突软骨及软骨下骨损伤动物模型后置入激活后的PRP;手术组（10只）建立髁突软骨及软骨下骨损伤动物模型;假手术组（10只）除不造成软骨及软骨下骨损伤外,其余与手术组相同。术后6周、12周对动物头颅进行螺旋CT扫描,采集SPCC格式数据。利用Materialise Proplan CMF 3.0软件对硬组织进行三维重建并分离上下颌骨,完整显露髁突的形态,确定标志点、参考平面及相应的测量指标,对测量结果进行统计学分析。结果　各个时间点手术组动物各项测量指标的测量值均小于假手术组与PRP修复组动物的（P < 0.05）;术后6周,PRP修复组动物的下颌升支高度、髁突长度、髁突宽度测量值均小于假手术组的（P < 0.05）;PRP修复组动物的下颌体长度、髁突高度测量值与假手术组动物的相比差异无统计学意义（P > 0.05）;术后12周PRP组动物的下颌升支高度、下颌体长度测量值均小于假手术组动物的（P < 0.05）,PRP修复组动物的髁突高度、髁突长度、髁突宽度测量值与假手术组动物的差异无统计学意义（P > 0.05）。结论　生长期髁突软骨损伤后,下颌骨生长发育相对停滞,髁突发生吸收。激活后的PRP可有效修复生长期髁突软骨损伤,维持下颌骨的正常形态,促进下颌骨及髁突的正常生长发育。     

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??Objective??An animal model of condylar cartilage and subchondral bone injury during growing period is established??and three-dimensional measurement of mandibular was performed with Materialise Proplan CMF 3.0 software to investigate the effect of PRP on repairing condylar cartilage and maintaining mandibular growth in growing period. Methods??Thirty growing New Zealand white rabbits were randomly divided into three groups. The PRP group animals ??10?? were implanted in activated PRP after the establishment of the animal model of condylar cartilage and subchondral bone injury.The condylar cartilage and subchondral bone injury models were established in the operation group ??10??. The sham operation group ??10?? was similar to the operation group except for the condylar cartilage and subchondral bone injury. At 6 and 12 weeks after surgery the animals received spiral computed tomography??and SPCC data were collected.Maxillary and mandibular three-dimensional reconstruction was performed using Materialise Proplan CMF 3.0. The upper and lower jaws were separated and the morphology of condylar was completely revealed. The result of measurement are analysed with statistical method after the determining the marking points??reference planes and corresponding measurement indexes. Results??The indexes of the operation group were all smaller than those of the sham operation group and the PRP group at each time point??P < 0.05????6 weeks after surgery??the height of mandibular ramus??the length of condyle and the width of condyle in PRP group were less than those in sham operation group??P < 0.05??. There was no significant difference in mandibular length or condylar height between PRP group and sham operation group ??P > 0.05??. The mandibular ramus height and mandibular body length in PRP group were less than those in sham operation group at 12 weeks after operation??P < 0.05??. There was no significant difference in condylar height??length or width between PRP group and sham operation group ??P > 0.05??. Conclusion??After the injury of mandibular condylar cartilage??the growth and development of mandibular are relatively stagnant??and the mandibular condyle is absorbed. Activated PRP can effectively repair the injury of condylar cartilage during growing period??promote the normal growth and development of mandible and condyle??and maintain the normal shape of mandible.     

Mandibular functional positioning only in vertical dimension contributes to condylar adaptation evidenced by concomitant expressions of L-Sox5 and type II collagen

OBJECTIVE: Concerted expressions of L-Sox5 and type II collagen play an important part in osteogenic transition in epiphyseal cartilage. This study was designed to elucidate the role of mandibular vertical functional positioning in condylar adaptive remodelling by examining L-Sox5 and type II collagen expressions in condylar cartilage. DESIGN: 40 female Sprague-Dawley rats at age of 5 weeks were randomly divided into the experimental (n=20) and control groups (n=20). Bite plates were fitted on the upper posterior teeth of the experimental animals to induce functional repositioning of mandible in vertical dimension. The animals in both experimental and matched control groups were sacrificed on days 3, 6, 9 and 12, respectively. Tissue sections were cut in the sagittal plane through the mandibular condyles and processed with histomorphological examination for cellular response and immunohistochemical test for expressions of L-Sox5 and type II collagen. Quantitative assessment was conducted with computer-assisted imaging system to reveal the correlation between these two factors. RESULTS: (1) Both L-Sox5 and type II collagen were expressed in prechondroblastic cells and chondroblastic cells. (2) When mandible was downward positioned, the amount of L-Sox5 expression was significantly higher by 16.1% (day 9) and 24.2% (day 12) than that of the control (P<0.05); Similarly, type II collagen expression in the experimental group was also significantly stronger by 9.3% (day 9) and 12.3% (day 12) than control group (P<0.05), indicating an enhanced osteogenic transition occurring in condylar cartilage. (3) There was a similarity in temporospatial patterns between the expressions of these two factors, indicating their integral functions in facilitating condylar adaptation. CONCLUSIONS: It is suggested that L-Sox5 plays a key role in adaptive remodelling of condylar cartilage resulting from downward positioning of the mandible. Integration with type II collagen enables L-Sox5 to induce osteogenic transition and consequently to encourage endochondral ossification.     

Induction of traumatic temporomandibular joint ankylosis in growing rats: a preliminary experimental study

Abstract –  There are many reports on the management of pediatric temporomandibular joint (TMJ) ankylosis. However, few authors have investigated the etiology of this disease in children. The purpose of this study was to determine the role of damage to both the condylar cartilage and disk in the induction of traumatic TMJ ankylosis during the growth period. The study was performed in growing rats by a common condyle fracture model. Intentional damage was performed to both the disk and condylar cartilage in the experimental group ( n  = 12), while the disk and condylar cartilage in the control group was left untouched ( n  = 12). Sham-operated growing rats were deemed the blank group ( n  = 10). Two rats from the experimental group and two from the control group were killed 24 h after the operation, and the result following surgical intervention was observed. Each rat's body weight in the three groups was monitored and recorded at 1, 2, 4, 6, 8, 10, and 12 weeks after surgery. Twelve weeks after the operation, all animals were killed. The prognosis was compared by mandible deviation measure, body weight evaluation, and histological observation. Animals from the experimental group presented a slow body weight increase and obvious mandible deviation while all involved TMJs showed fibrous ankylosis in various degrees. The damage to both the condylar cartilage and disk in the condylar fracture might play a vital role in traumatic TMJ ankylosis development during the growth period. The results of this study suggest that more attention should be paid to condylar fractures in children that are accompanied with severe cartilage and disk damage, which is a matter of significance for pediatric TMJ ankylosis prevention.     

下颌骨髁突不同类型骨折钛板内固定手术治疗相关影响因素分析

目的：分析下颌骨髁突不同类型骨折进行钛板内固定手术及其影响术后并发症的相关因素,为以后下颌骨髁突骨折治疗总结经验以便更好的为患者服务。方法：收集温州医科大学附属口腔医院2003年4月~2012年4月手术完成的下颌骨髁突骨折行钛板内固定患者,手术前后复查对比下颌骨全景片、下颌骨平扫CT、下颌骨矢状CT及颅颌三维CT重建。依据下颌骨骨折部位分为髁突囊内骨折,髁突颈部骨折,髁突基部骨折3组,对3组骨折术后患者的咬合状况、开口度、面神经功能等恢复情况进行回顾性分析。结果：210例随访病例中,术后咬合关系恢复不良30例;螺钉松动57枚,钛板断裂0例,面神经颧支损伤15例,面神经颞支损伤30例,张口受限伴下颌运动曲线患侧偏斜35例。结论：解剖手术能力或者面神经的个体变异;创口感染;不适当的应力集中、钛板和螺钉的位置、数量及固定部位,颌间牵引,关节周围相关软组织复位状况等为影响下颌骨髁突骨折坚强内固定手术并发症相关因素。     

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.     

Differences in biologic response of the mandibular condyle to forward traction or opening of the mandible An experimental study in the rat

The effect of different mandibular postures on the growth of the mandible was studied. A total of 60 female Wistar rats were divided into 3 groups, and all the animals were anesthetized for 6 h daily from the age of 30 days onwards. The first group served as controls. The second had the mandible maintained in a protracted position, and the third had the mandible in an open position during the anesthesia. Macroscopic measurements showed the growth of the mandibular condyle to be increased in a posteroinferior direction and also in a superior direction in the animals with the mandible in an open position. The cartilage layer containing collagen type II was significantly thinned, whereas cell proliferation had significantly increased in the posterosuperior region. In association with mandibular protrusion the thickness of the cell layer containing collagen type II had increased, and cell proliferation in the posterosuperior region had significantly decreased. Significant differences in the growth of the condylar process were observed histologically and histochemically between the experimental animals, implying that the most rewarding aspect of the regulation of condylar growth seems to be the possibility to regulate the maturation rate of the cartilage cells.     

The role of the disc in the healing of displaced subcondylar fracture in the growing period: an experimental study in rats

The purpose of this study was to evaluate the role of the disc in the healing of condylar fractures in the growing period. 40 growing and adult male Wistar rats were randomized into 4 equal groups: growing rats suffering condylar fracture with disc damage; growing rats suffering condylar fracture without disc damage; adult rats suffering condylar fracture with disc damage; adult rats suffering condylar fracture without disc damage. 3 months after the operation all animals were killed and the outcomes were compared using mandible deviation measure, body weight evaluation and histological observation. In growing rats, when the disc was undamaged maintaining its relation to the condyle head, even though the condylar fractured fragment was displaced, the condyle healed and recovered almost to normality in 3 months. In the same condyle fracture form, once the disc was damaged and lost the normal relation with the condyle head, the outcome was unfavourable. The occurrence of damage to the disc and its attachment to the condyle head are important factors in the healing of condyle fractures in the growing period.     

Involvement of PI3K/Akt pathway in rat condylar chondrocytes regulated by PTHrP treatment

Objective

The aim of this study was to explore the mutual communication of the parathyroid hormone-related peptide (PTHrP) and phosphatidylinositol 3-kinase/threonine protein kinase (PI3K/Akt) pathway on the proliferation and differentiation of condylar chondrocytes from Sprague-Dawley (SD) rats.

Methods

Condylar chondrocytes from the condylar cartilage were cultured and an organ culture system of mandibular condyles was employed. The distribution of PI3K, phospho-Akt (p-Akt), and PTHrP in condylar cartilage was detected by either immunohistochemistry or immunofluorescence. The second passage chondrocytes and condyle specimens in the organ culture system were treated with PTHrP, LY294002, PTHrP and LY294002 in combination, or dimethyl sulfoxide (DMSO), separately. The mRNA and protein levels of type II (Col II) and type X collagen (Col X) were investigated by real-time polymerase chain reaction (PCR) and Western blot analysis. The condyle growth in organ culture system was analysed by haematoxylin–eosin staining.

Results

PTHrP, PI3K, and p-Akt were mainly located in the proliferative and hypertrophic zones. PTHrP promoted the proliferation of condylar chondrocytes, while LY294002 limited this effect. The mRNA and protein levels of Col II and Col X in these cells were reduced by PTHrP and enhanced by LY294002. Organ culture showed a significant enhancement of condyle elongation with PTHrP treatment or a combination of PTHrP and LY294002 treatment. After treatment with LY294002, the length of condyles was reduced compared with the samples treated with DMSO.

Conclusions

We conclude that the PI3K/Akt pathway plays an essential role in the proliferation and differentiation of condylar chondrocytes and is a potential target for PTHrP in regulating chondrocyte differentiation at condylar cartilage.     

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.     

单侧前牙反牙合大鼠髁突异常分化的软骨细胞中CaMKⅡ的表达变化

目的:研究实验性单侧前牙反牙合(unilateral anterior crossbite,UAC)对大鼠髁突软骨的致病意义及对促软骨细胞分化的CaMKⅡ表达的影响。方法:40只6周龄SD雌性大鼠,随机等分为UAC组和对照组,其中UAC组左侧上下切牙各戴一套筒冠并形成反牙合关系,对照组不作处理。于实验开始后4周和8周取材,HE和番红O染色观察髁突软骨的组织形态变化,免疫组织化学染色观察CaMKⅡ的表达,Real-time PCR测量相关基因表达水平的变化。结果:UAC组髁突软骨细胞分化异常,软骨变薄,基质减少,且随时间的延长而加重(P<0.05),CaMKⅡ阳性细胞百分数以及CaMKⅡ和Mmp-13的mRNA表达水平上调,但促增殖的Pcna以及软骨基质Col2a1、 Aggrecan的mRNA的表达水平下调。结论:UAC可导致髁突软骨异常分化并伴有CaMKⅡ的高表达。     

Expression of type X collagen and capillary endothelium in condylar cartilage during osteogenic transition--a comparison between adaptive remodelling and natural growth

Adaptive remodelling of the condylar cartilage in response to mandibular protrusion constitutes the rationale for bite-jumping appliances to solicit growth modification. By investigating the expression of type X collagen and capillary endothelium, this study was designed to evaluate the osteogenic transition of chondrogenesis during adaptive remodelling of condylar cartilage and compare it with that under natural condylar growth. One hundred female Sprague-Dawley rats, 35 days of age, were divided into five experimental groups (n = 15, fitted with bite-jumping appliances) where condylar adaptation was created by forward repositioning of the mandible, and five control groups (n = 5) where the condyles underwent natural growth. The animals were sacrificed at 3, 7, 14, 21 and 30 days and 7 mum serial sections of the condyles were processed for in situ hybridization and immunohistochemical analyses. The expression of type X collagen in the hypertrophic zone and capillary endothelium in the erosive zone of condylar cartilage were examined to evaluate osteogenic transition, a critical programme leading to endochondral ossification. The results showed that (1) The temporal pattern of the expression of type X collagen and capillary endothelium during condylar adaptation coincided with that during natural condylar growth. (2) The amount of the expression of these two factors during condylar adaptation was significantly higher than that during natural growth (P < 0.001). It is suggested that condylar adaptation in growing rats triggered by mandibular forward positioning enhances osteogenic transition which eventually results in increased bone formation.     

Mandibular advancement using a retrocondylar cartilage graft: a 20-year prospective study

We examined the outcome after a mean of 46 months (range 18-204) of 73 patients with severe mandibular retrusion who had surgical advancement of the mandible by a post-condylar cartilage graft. The extent of the mandibular advance and the change in position of the condyle were measured by a previously described cephalometric method. Tomograms of the temporomandibular joint (TMJ) were taken at defined intervals and any changes in the articulation recorded. The mandible was advanced by a mean (S.D.) of 9.8 (3.4) mm. The mean postoperative change recorded on the final cephalometric radiograph was 0.4 (4.7) mm forward (95% CI -0.70 to+1.50). The mandibular condyle was advanced horizontally by a mean 7.2 (2.1) mm and depressed vertically by a mean of 5.9 (2.6) mm. postoperatively the condyle relapsed horizontally by a mean of 1.5mm and moved vertically downward by a mean of 0.2mm. Eleven patients had substantial skeletal relapse. Eight patients were regarded as clinical failures. Skeletal relapse did not always lead to clinical failure because of compensatory mandibular growth. Changes in the condylar region, which contributed to relapse, included condylar absorption and remodelling (n=7) and absorption of the cartilage graft (n=6). There were no postoperative functional problems with the TMJ. We conclude that the post-condylar cartilage graft is a useful technique for the treatment of certain cases of mandibular retrusion. The postoperative morbidity was less than that reported after other techniques of mandibular advancement including distraction. Skeletal relapse was found in more cases than clinical results had suggested.     

两种异常咬合刺激对小鼠髁突影像及组织形态学影响研究

目的 探究异常咬合刺激对小鼠髁突影像及组织形态学影响.方法 选取6周龄雌性C57BL/6J小鼠36只,根据饲养时间(3、7周)均分小鼠后,再随机分为对照组、单侧前牙反(unilateral anterior crossbite,UAC)组和双侧前牙咬合抬高(bilateral anterior elevation,B...     

Skeletal changes after experimentally displaced condylar process fracture in growing rats.

INTRODUCTION: Fractures of the mandibular condyle are common. A potential for growth disturbances in young individuals has been reported; however, there are few experiments studying such consequences. Skeletal changes after fracture of the condyle in the growing period were analysed in this study. MATERIAL: Fifty young Wistar rats weighing 100g were used. Under general anaesthesia unilateral fracture dislocations of the condylar process were induced surgically in the experimental group (n=25), while only surgical access was performed in the sham-operated group. The animals were sacrificed at 3 months of age. The mandibles were disarticulated, and radiographs were taken (axial skulls and lateral hemimandibles). Cephalometric evaluations were made using a computer system. Statistical tests were applied between groups and contralateral sides in each group. RESULTS: There were atrophy and degenerative change of the fractured condylar process. There was also a significant difference in the height of the mandibular body and in the length of anterior and posterior maxilla. CONCLUSION: It was concluded that an experimental fracture of the mandibular condyle during the growing period in rats induced degenerative changes of the condyle as well as an asymmetry of the mandible, affecting height of the body, also leading to consequences in the maxilla.     

下颌持续前导对成年大鼠髁突软骨骨形态发生蛋白表达及超微结构的影响

目的 观察成年期大鼠在下颌持续前导作用下髁突软骨的改建以及超微结构的变化。方法 将30只9周龄SD大鼠随机分为实验组和对照组,实验组佩戴上颌斜面导板,对照组不做任何处理,分别在第3、7、14、21、30天处死动物并取材,免疫组织化学染色检测骨形态发生蛋白2（BMP-2）在髁突中的表达及分布,透射电镜观察髁突软骨细胞的超微结构,Micro CT分析髁突骨质的变化。结果 与对照组相比,实验组髁突中部和后部软骨增生明显,软骨细胞BMP-2阳性细胞率及灰度值在第7天开始增多,随时间延长而增强,髁突软骨细胞的超微结构出现细胞核固缩,核周微丝变少、脂滴变小、内质网腔隙肿胀、细胞外基质增宽变多等。Micro-CT显示实验组的新生骨和骨小梁厚度、骨小梁数量和分离度随时间延长而增加。结论 在下颌持续前导下,成年期大鼠髁突软骨出现增生性改建,并存在BMP-2的高表达。