Installing and thereafter removing an aberrant prosthesis elicited opposite remodelling responses in growing mouse temporomandibular joints

Temporomandibular joint (TMJ) displays a high remodelling capability. The current purpose was to investigate the differences between mandibular condylar remodelling responses of growing mice to installation and removal of unilateral anterior crossbite (UAC) prosthesis. Twenty‐four mice were divided into one mock control group and two UAC groups. Unilateral anterior crossbite was created by installing a pair of prosthesis to left‐side maxillary and mandibular incisors. Unilateral anterior crossbite was removed in removal group at 3 weeks but remained in UAC group. Temporomandibular joints were sampled at 7 weeks. Changes in condylar cartilage and subchondral bone were assessed by histology and in vivo micro‐CT. Real‐time PCR and immunohistochemistry were performed to evaluate expression changes in ADAMTS‐5, MMP‐3, MMP‐9, MMP‐13, IL‐1, TNF‐α, OPG and RANKL. Statistical analysis was performed at α = 0·05. Temporomandibular joint cartilage degradation was induced by UAC as previously reported but was reversed by removal of UAC. The dropped cartilage thickness, chondrocyte number and collagen II‐positive area, the increased expression levels of Adamts‐5, Mmp3, 9, 13, Tnf‐α and Il‐1β in cartilage, the decreased ratio of OPG/RANKL in both condylar cartilage and subchondral bone, the loss of TMJ subchondral bone and the increase in the TRAP‐positive cells in subchondral bone were all reversed in the removal group (P < 0·05). The growing mouse TMJ condyle displays a high remodelling capability which can be degenerative and rehabilitative, respectively, in response to placement and thereafter removal of the aberrant prosthesis. Eliminating aberrant prosthesis is helpful to promote the degraded condyle to recover.     

Condyle and mandibular bone change after unilateral condylar neck fracture in growing rats

Unilateral fracture of the condylar neck in immature subjects might lead to mandible asymmetry and condyle remodelling. A rat model was used to investigate mandibular deviation and condylar remodelling associated with condyle fracture. 72 4-week-old male rats were randomly divided into three groups: an experimental group (unilateral transverse condylar fracture induced surgically), a sham operation group (surgical exposure but no fracture), and a non-operative control group (no operation). The rats were killed at intervals up to 9weeks after surgery, and outcomes were assessed using various measures of mandible deviation, histological and X-ray observation, and immunohistochemical measures of expression levels of connective tissue growth factor (CTGF) and type II collagen (Col II). The fracture led to the degeneration of mandibular size, associated with atrophy of fractured condylar process. Progressive remodelling of cartilage and increasing expression levels of CTGF and Col II were found. The authors conclude that condylar fracture can lead to asymmetries in mandible and condyle remodelling and expression of CTGF and Col II in condylar cartilage on both the ipsilateral and the contralateral sides.     

单侧前牙反牙合对大鼠下颌髁突软骨内CaR、PTHrP表达的影响研究

目的　探索单侧前牙反牙合（unilateral anterior crossbite,UAC）对大鼠下颌髁突软骨内钙离子敏感受体（calcium-sensing receptor,CaR）、甲状旁腺激素相关蛋白（parathyroid hormone-related protein,PTHrP）分子表达以及软骨细胞增殖和发育的影响。方法　选择6周龄雌性SD大鼠48只,根据实验时间点（2、4、8周）随机分为3大组,每大组再随机分为2组（对照组、UAC实验组）,每组动物数量8只。对SD大鼠施加UAC刺激,于2、4、8周后分别处死各组大鼠,对颞下颌关节软骨进行CaR、PTHrP、PTHrP 受体（PPR）分子的免疫组化染色,提取软骨内mRNA进行增殖标志分子、软骨细胞表型分子和终末分化相关分子的Real-time PCR检测。结果　UAC实验组大鼠髁突软骨2周时即开始出现CaR的表达增高,4周时继发有PTHrP的表达上调,但是其惟一受体PPR的表达从2周时即显著降低;增殖标志分子和软骨细胞表型分子的表达从2周时开始显著降低,终末分化相关分子的表达从4周开始显著增高。结论　UAC可导致下颌髁突软骨内CaR、PTHrP表达改变,进而影响软骨细胞的增殖和分化状态。     

实验性单侧前牙反牙合修复体对大鼠髁突软骨中甲状旁腺激素相关蛋白和PTH/PTHrP受体-1表达的影响

目的 探讨实验性单侧前牙反牙合修复体对大鼠髁突软骨中甲状旁腺激素相关蛋白（PTHrP）及PTH/PTHrP 受体-1（PTH1R）表达的影响。方法 在6周龄SD大鼠左侧上、下切牙粘接金属不良修复体,使其呈反牙合关系,2、 4、8周后取颞下颌关节（TMJ）,苏木精-伊红（HE）染色观察组织形态学变化,免疫组织化学染色及实时定量聚合酶链反应检测PTHrP、PTH1R的表达情况。结果 8周时,实验组髁突软骨出现明显退行性变,PTHrP阳性细胞较对照组显著增多（P<0.01）, PTH1R阳性细胞明显减少（P<0.01）;实验组髁突软骨PTHrP mRNA的表达显著高于对照组（P<0.01）,而PTH1R mRNA表达明显降低（P<0.01）。结论 髁突软骨PTHrP的高表达因PTH1R的低表达不能有效发 挥作用,可能是髁突软骨骨关节病样变的重要分子机制之一。     

Ihh signaling regulates mandibular symphysis development and growth

Symphyseal secondary cartilage is important for mandibular development, but the molecular mechanisms underlying its formation remain largely unknown. Here we asked whether Indian hedgehog (Ihh) regulates symphyseal cartilage development and growth. By embryonic days 16.5 to 18.5, Sox9-expressing chondrocytes formed within condensed Tgfβ-1/Runx2-expressing mesenchymal cells at the prospective symphyseal joint site, and established a growth-plate-like structure with distinct Ihh, collagen X, and osteopontin expression patterns. In post-natal life, mesenchymal cells expressing the Ihh receptor Patched1 were present anterior to the Ihh-expressing secondary cartilage, proliferated, differentiated into chondrocytes, and contributed to anterior growth of alveolar bone. In Ihh-null mice, however, symphyseal development was defective, mainly because of enhanced chondrocyte maturation and reduced proliferation of chondroprogenitor cells. Proliferation was partially restored in dual Ihh;Gli3 mutants, suggesting that Gli3 is normally a negative regulator of symphyseal development. Thus, Ihh signaling is essential for symphyseal cartilage development and anterior mandibular growth.     

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。     

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.     

Effect of occlusal (mechanical) stimulus on bone remodelling in rat mandibular condyle

Gazit D, Ehrlich J, Kohen Y, Bab I. Effect of occlusal (mechanical) stimulus on bone remodelling in rat mandibular condyle. J Oral Pathol 1987: 16: 395–398.
Mechanical load influences the remodelling of skeletal tissues. In the mandibular condyle, occlusal alterations and the consequent mechanical stimulus induce changes in chondrocytes and cartilage mineralization. In the present study we quantified in the mandibular condyle the effect of occlusal interference on remodelling of the subchondral bone. Computerized histomorphometry after 5–21-day exposure to the influence of a unilateral occlusal splint revealed an increased rate of trabecular remodelling, consisting of enhancement in osteoblast and osteoclast numbers and activities. The bone formation parameters reached their high values on Days 5 or 9 and remained stable thereafter. Bone resorption showed a gradual increase throughout the experimental period. These results further characterize the temporomandibular joint reaction to occlusal alterations. It is suggested that the present increase in bone turnover together with the known enhancement in chondrogenesis are part of a process of functional adaptation in response to mechanical stimulus.     

Histological evaluation of condylar hyperplasia model of rabbit following distraction osteogenesis of the condylar neck

Summary Condylar hyperplasia is the excessive unilateral growth of mandibular leading to facial asymmetry, occlusal disturbance, joint pain and dysfunction. The aim of this study is to evaluate the histological presence of temporomandibular joint in model of condylar hyperplasia by lengthening unilateral condylar neck of distraction osteogenesis. An extra oral distractor was employed to achieve unilateral condylar neck distraction (1·0 mm daily for 7 days). The experimental condylar necks were elongated by 7 mm compared to the contralateral. Eleven adult white rabbits were used. Eight rabbits were, respectively, sacrificed after the post‐distraction period (4 or 8 weeks). All animals were evaluated clinically and histomorphometrically. The condyles radiologically showed remodelling, flattening and sclerosis. In 4‐week group, thinning of the cartilage was evident, and the trabeculae were long, not multiply connected. A thin, dense fibrous layer covered all over the surface of cartilage. In 8‐week group, the cartilaginous layer was similar to thickness of the normal cartilage, but still thinner than control. However, the fibrous layers covering condyle manifested slight degenerative changes, and even depressions and erosions were seen in the cartilage and subchondral bone. The trabeculae showed denser and multiply connected. In 8‐week group, the cartilaginous thickness of surgical condyles was significantly thinner than the contralateral. This study indicates that unilateral distraction of condylar neck loads the condyles asymmetrically. Asymmetrical loads affect more on the surgical condyles than the contralateral, and after 8 weeks of the post‐distraction, condyle could recover from asymmetrical loads in some degree.     

抑制p38 MAPK对小鼠釉质发育相关基因表达的影响

目的 研究p38丝裂原活化蛋白激酶(p38 mitogen activated protein kinase,p38 MAPK)对成釉上皮中釉质发育相关基因表达的影响,为釉质发育分子机制的研究提供基础.方法 在体外小鼠下颌磨牙牙胚的培养基中加入以DMSO溶解的p38 MAPK特异性抑制剂SB203580为实验组,以培养...     

氯通道阻断剂NPPB对鸡喙外胚间充质细胞增殖分化影响的研究

目的 氯离子通道阻断剂NPPB对鸡喙外胚间充质细胞(chicken mandibular mesenchymal cells,CMMC)增殖及分化能力的影响。方法 应用MTT、实时定量PCR的方法,观察NPPB阻断氯离子通道后,鸡喙外胚间充质细胞在AA-BGP诱导成骨过程中,细胞增殖及Sox9mRNA、Runx2mRNA及Col10mRNA的表达的变化。结果 在AA-BGP诱导组及无AA-BGP诱导组,NPPB均抑制了CMMC的增殖(P<0.05)。在AA-BGP诱导组及无AA-BGP诱导组,NPPB下调Col10mRNA及Runx2mRNA的表达水平均有显著性差异(P<0.05),Sox9mRNA的表达水平没有显著改变。结论 阻断氯离子通道可抑制鸡喙外胚间充质细胞增殖,并影响细胞向肥大化的软骨细胞分化,可能通过调节Runx2水平影响分化。     

Effect of occlusal (mechanical) stimulus on bone remodelling in rat mandibular condyle

Mechanical load influences the remodelling of skeletal tissues. In the mandibular condyle, occlusal alterations and the consequent mechanical stimulus induce changes in chondrocytes and cartilage mineralization. In the present study we quantified in the mandibular condyle the effect of occlusal interference on remodelling of the subchondral bone. Computerized histomorphometry after 5-21-day exposure to the influence of a unilateral occlusal splint revealed an increased rate of trabecular remodelling, consisting of enhancement in osteoblast and osteoclast numbers and activities. The bone formation parameters reached their high values on Days 5 or 9 and remained stable thereafter. Bone resorption showed a gradual increase throughout the experimental period. These results further characterize the temporomandibular joint reaction to occlusal alterations. It is suggested that the present increase in bone turnover together with the known enhancement in chondrogenesis are part of a process of functional adaptation in response to mechanical stimulus.     

活化转录调控因子2(ATF-2)在下颌骨髁突软骨细胞中调控bcl-2机制的研究

目的:研究ATF-2通过bcl-2影响髁突软骨生长发育的机制.方法:应用体外培养原代小鼠髁突软骨细胞,原代细胞基因转染,蛋白印迹杂交等技术,阐明ATF-2调控bcl-2表达的机制.结果:外源性的ATF-2在髁突软骨细胞中,与bcl-2的调控子中CRE结合,增强bcl-2调控子的活性;当CRE位点的序列改变,ATF-2不能在髁突软骨细胞中对bcl-2调控子的活性产生影响.结论:ATF-2在软骨细胞中,通过影响有凋亡抑制作用的bcl-2的活性和表达,参与下颌骨髁突软骨的生长发育.     

The PI3K/Akt signalling pathway may play an internal role related to abnormal condylar growth: a preliminary study

Developmental deformity of the mandible is one of the most common craniofacial malformations and is closely related to abnormal condylar growth. In this study, the role of PI3K/Akt signalling in the regulation of chondrocyte proliferation and hypertrophic differentiation in the condylar cartilage was studied. Immunohistochemical staining was used to investigate the expression of PI3K and p-Akt in the rat condyle cartilage. Rat condylar chondrocytes were cultured for the investigation of chondrocyte proliferation and hypertrophic differentiation when PI3K/Akt was inhibited. In addition, organ culture of the rat mandibular condyle was performed to evaluate the condyle cartilage growth while PI3K/Akt was inhibited. PI3K-positive cells and p-Akt-positive cells showing cytoplasmic staining were found to be present in the condylar cartilage. Reduced cell proliferation was observed in the culture of rat condylar chondrocytes when PI3K/Akt was inhibited; however, the hypertrophic differentiation level was increased. The proliferative zone thickness of condylar cartilage in the experimental group was less than that in the control group (P = 0.00185), but the hypertrophic zone was greater than that in the control group (P = 0.01048). PI3K/Akt signalling exerts opposite influences on chondrocyte proliferation and hypertrophic differentiation of the condylar cartilage, and these data suggest that PI3K/Akt is a potential intracellular regulation signal pathway in condylar cartilage development.     

Interleukin-1 beta affects cyclooxygenase-2 expression and cartilage metabolism in mandibular condyle

Extracellular matrix degradation in mandibular condylar cartilage is mediated by various cytokines in the temporomandibular joint (TMJ). Interleukin-1 beta (IL-1β) is detected in joint structures with pathologic status, and participates in catabolic action in the extracellular matrix. The purpose of this study was to investigate the effects of IL-1β on cyclooxygenase-2 (COX-2) expression and cartilage metabolism using cultured chondrocytes from mandibular condyle. Articular chondrocytes from the porcine mandibular condylar cartilage around the surface were cultured and treated with 0–10 ng/ml IL-1β or 0–1000 ng/ml prostaglandin (PGE₂) for 0–24 h. The mRNA levels of COX-2, MMP-1, -3, and -13 were evaluated by real-time PCR analysis. The protein levels of PGE₂ and MMPs were examined by ELISA and Western blot analysis, respectively. The expression levels of COX-2 and PGE₂ were enhanced by exogenous IL-1β in chondrocytes. The mRNA levels of MMP-1, -3, and -13 were up-regulated by PGE₂ treatment dose-dependently. It is shown that the expression of COX-2/PGE₂ was enhanced by IL-1β in articular chondrocytes from mandibular condyle, and that MMP-1, -3, and -13 were induced by PGE₂, suggesting that IL-1β-induced COX-2/PGE₂ play a crucial role in catabolic processes of mandibular condylar cartilage under inflammatory conditions.     

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...     

单侧后牙反者髁突侧向运动轨迹的研究

目的通过记录单侧后牙反者与正常者下颌侧向运动时髁突在三雏方向上的运动轨迹。探讨单侧后牙反者髁交侧向运动轨迹的特征。揭示其与正常之间的差异。方法正常15例,单侧后牙反7例．应用计算机化的髁突运动轨迹描记仅(computer-Aide,Axiography,CADlAX)Ⅰ型以及分析软件(Gamma Dental Sofrware for Windows 2．3．2．22。GDSW)记录下颌做左右侧向运动时髁突在水平面及矢状面上的运动轨迹。结果实验组侧向运动中非工作侧矢状向最大位移量王著小于正常对照组。工作侧髁突向后运动的幅度大于正常对照组。结论单侧后牙反者髁突侧向运动轨迹形态与正常有明显差异。其两侧关节囊、韧带松驰。     

Can electrocautery of the mandibular condyle effectively treat condylar hyperplasia?

This study aims to introduce and evaluate a novel technique to treat unilateral condylar hyperplasia (UCH) by electrocauterization of the mandibular condyle via an intraoral approach.Patients suffering from unilateral condylar hyperplasia (UCH) were included in this study. All patients underwent electrocauterization of the affected condyle. An intraoral incision on the anterior border of the mandibular ramus was made to expose the external surface of the ramus and access the anterior border of the condylar head. A hole was then drilled into the condyle and cauterization was performed; six patients also received orthognathic surgery during the procedure. Patients underwent careful clinical assessment and radiological evaluation including panoramic view, lateral and posteroanterior cephalometry, cone-beam computed tomography (CBCT) and scintigraphy to assess condylar growth for a period of 12–24 months. Ten patients (5 male and 5 female) with active UCH type 1B or 2A were included in this study with a mean age of 20.7 years (range, 18–21.7 years). At the 12-month postoperative assessment, clinical evaluation showed stable dental occlusion with no midline shift; scintigraphy showed persistently reduced cellular activity, and computed tomography scans revealed no degeneration in either of the condyles with complete healing of the drilled holes.Within the limitations of this study it seems that the proposed treatment approach might be an alternative to previously established protocols.