输送盘牵张成骨术重建下颌髁突后对下颌骨生长发育的影响

目的:研究输送盘牵张成骨术重建下颌髁突后对下颌骨生长发育的影响.方法:选用3～4 月龄健康幼年雄性山羊16 只,手术切除右侧髁突(保留关节盘),在右下颌升支行反"L"形骨切开术形成骨输送盘,并安置牵张器.以每日2 次,每次0.4 mm的速率向上牵引输送盘至关节窝.在手术后当天、牵张结束后当天、牵张结束后4、12、24、48 周时行三维CT检查评价输送盘改建及牵张间隙内新骨形成情况,并分别于12、24、48 周3 个时间点各处死动物2 只对新生髁突做组织学检查.牵张结束后48 周时处死剩余10 只动物,对下颌骨及重建髁突形态进行观察与测量.左侧下颌骨作为正常对照组.结果:三维CT显示新生髁突形态逐渐改建并接近正常髁突,牵张间隙新骨生成良好.大体观察发现新生髁突体积较正常侧明显增大,但下颌骨的生长与正常侧无显著差异.新生髁突表面有一层纤维软骨覆盖,组织学结构与正常关节软骨类似.结论:输送盘牵张成骨重建髁突未对下颌骨的生长发育产生明显影响;下颌运动产生的功能刺激是下颌骨继续生长发育的主要原因.     

髁突骨软骨瘤与髁突增生患者的CT表现特点分析

目的:比较下颌骨髁突骨软骨瘤和单侧下颌骨髁突增生的CT表现特点。方法:对2005—2010年上海交通大学医学院附属第九人民医院口腔颌面外科收治的下颌骨髁突骨软骨瘤11例和单侧下颌骨髁突增生8例患者的CT影像学资料进行评价,评价指标包括病变髁突大小、病变范围以及病变周围软硬组织改变。结果:11例下颌骨髁突骨软骨瘤病例CT显示肿瘤与病变髁突无明显分界(8/11)或与患侧髁突有蒂相连(3/11);肿瘤骨皮质及骨髓腔均与患侧髁突相续,瘤体表面均有特征性薄层软骨帽覆盖,瘤体外周密度通常高于中心;瘤体周围均有薄层软组织包绕。患侧颞骨关节面表面均有明显矿化,且因受瘤体压迫改建而较对侧平坦,患侧关节上、下腔间隙较对侧明显变窄;肿瘤生长方向不尽相同。8例单侧下颌骨髁突增生病例CT显示髁突颈部和(或)下颌支延长,髁突形状改变;增生的髁突外周骨皮质均有不同程度的骨化,硬化层厚度较对侧大;骨髓腔密度较不均匀。结论:CT检查能有效提供病变髁突及其周围软硬组织情况,为鉴别诊断下颌骨髁突骨软骨瘤和单侧下颌骨髁突增生提供良好的依据。     

甲状旁腺激素相关蛋白在下颌骨髁突软骨生长发育中的作用机制

下颌骨髁突软骨是一种继发性纤维性软骨,其生长发育的调控过程可能更加复杂.近十几年来,国内外才渐有针对髁突软骨生长发育研究的相关报道.甲状旁腺激素相关蛋白(parathyroid hormone related protein,PTHrP)是软骨代谢的关键调控因子,广泛参与软骨生长改建、形态发生及软骨内成骨的过程.同四肢软骨类似,PTHrP在下颌骨髁突软骨生长发育过程中亦发挥关键作用.深入了解PTHrP信号及相关因子在髁突软骨发育过程中的调节机制,可进一步明确PTHrP对颞下颌关节生长发育的影响,这对临床诊疗有重要指导意义.本文就PTHrP在下颌骨髁突软骨生长发育过程中的作用机制作一综述.     

继发性软骨与原发性软骨

下颌髁突软骨与身体其它部位的软骨不同，它是在种系发生个体发育过程中继发形成的，称为继发性软骨（ｓｅｃｏｎｄａｒｙ－ｔｙｐｅｃａｒｔｉｌａｇｅｓ），包括下颌髁突软骨、喙突软骨、下颌角软骨等，它既受局部因素的影响又受生长因素的影响。而长骨骺软骨、蝶枕软骨...     

透明质酸抑制下颌骨髁突软骨钙化的实验研究

目的：探究透明质酸（HA）对下颌骨髁突软骨钙化的影响及其机制。方法：取新生小鼠（3 d）的髁突软骨及长骨软骨分别置于空白（培养对照组）和加有 HA（HA 组）的培养基中行小组织块培养,分别培养6周后,HE、茜素红、碱性磷酸酶（ALP）染色观察2组软骨组织的钙化情况,免疫组化观察 VEGF、MMP-13蛋白表达情况。结果：培养对照组髁突软骨内观察到钙化、基质中 VEGF 和 MMP-13表达阳性以及阳性细胞较多。HA 组未观察到髁突和长骨软骨内成骨和钙化发生,但观察到软骨表面积的增大,VEGF 及 MMP-13在软骨细胞基质内表达阴性,阳性细胞率减少（P ＜0．05）。结论：在体外培养环境下,HA 可以抑制下颌骨髁突软骨钙化,其机制可能是抑制了 VEGF 及 MMP-13的表达。     

Fgf9在小鼠下颌骨发育软骨成骨及膜内成骨过程中的作用探讨

目的： 观察成纤维细胞生长因子9（fibroblast growth factor 9, Fgf9）基因敲除小鼠模型中下颌骨发育的骨质变化,探讨Fgf9参与下颌骨发育中的软骨成骨和膜内成骨的过程。方法： 建立Fgf9基因敲除小鼠模型（Fgf9^-/-）。利用显微CT技术检测Fgf9^-/-的下颌骨形态及骨参数,利用原位杂交对Fgf9在下颌骨的表达进行定位,应用H-E染色和番红固绿染色对胚胎的髁突、麦克尔软骨、膜内成骨区进行组织学分析。采用 SPSS 25.0软件包对数据进行统计学处理。结果： 显微CT显示,Fgf9^-/-髁突、喙突、下颌角区形态不佳,Tb.N降低、Tb.Sp增高、BMD下降。原位杂交显示,Fgf9广泛表达于软骨膜、软骨细胞、成骨细胞、血管内皮细胞及软骨及骨的周围间充质细胞。H-E染色与番红固绿染色显示, Fgf9^-/-髁突软骨形态畸形、软骨基质分泌不足、肥大软骨细胞比例下降、周围骨小梁纤细且分散。Fgf9^-/-麦克尔软骨前段软骨成骨及下颌骨体部的膜内成骨形成的骨小梁纤细、分散且矿化不良。结论： Fgf9在髁突软骨成骨过程中,促进软骨细胞分化成熟、分泌软骨基质,同时可能促进成骨细胞分泌骨基质,从而形成粗壮且健康的骨小梁。Fgf9参与膜内成骨,通过调控成骨细胞,促进骨小梁形成和矿化。     

过氧化物酶增殖活化受体γ对老龄鼠髁状突的影响

目的 通过给予过氧化物酶增殖活化受体γ(peroxisome proliferator-activated receptor γ,PPARγ)激动剂-吡格列酮,观察PPARγ对老龄鼠髁状突软骨及软骨下骨的影响.方法 18月龄健康雄性C57BL/6小鼠20只,随机分为两组,实验组每日予以吡格列酮灌胃20 mg/kg,对照组每日予以生理盐水灌胃.8周后处死动物取双侧下颌骨,行下颌骨X线检查及髁状突骨密度测定,同时行髁状突部位组织学观察,并采用骨形态计量学方法计算髁状突软骨下骨的静态骨参数.结果 实验组髁状突的X线片灰度值、骨密度、骨小梁面积百分率、骨小梁的平均宽度、胶原纤维及弹性纤维的含量均明显低于对照组.结论 PPARγ能抑制老龄鼠髁状突的成骨代谢及软骨的增殖和分化,促进其髁状突骨质疏松的发生、发展.     

透明质酸、TGF-β1对下颌骨髁突软骨增殖分化的影响

目的:研究透明质酸(HA)、TGF-β1因子对下颌骨髁突软骨增殖分化的影响.方法:取新生小鼠的下颌骨髁突软骨体外进行组织培养,按培养液内添加因子不同分为对照组、HA(0.5 mg/ml)、TGF-31(5 ng/ml)组,于培养1、2、4、6、8周后进行形态学观察、软骨面积测量、茜素红染色以及碱性磷酸酶染色研究.结果:对照组中髁突软骨在培养4周后软骨内开始出现高密度光阻射区,茜素红染色、碱性磷酸酶染色提示软骨基质出现了钙化、软骨内成骨的过程;HA组中髁突软骨内未出现高密度光阻射区,而髁突软骨面积却显著增大(P ＜0.05);TGF-β1组中髁突软骨在培养2周后提前出现了高密度光阻射区,然软骨面积无显著改变(P＞0.05).结论:在体外培养下,HA可以促进髁突软骨的增殖,对软骨细胞的肥大分化有一定的抑制作用,TGF-31在早期可显著促进髁突软骨细胞的肥大分化.     

下颌骨发生的研究进展

在胚胎发育期间,全身的骨架系统通过膜内成骨和软骨内成骨形成.膜内成骨主要形成颅面部的扁骨,而脊柱、四肢骨及部分颅面骨架通过软骨内成骨形成.下颌骨的发生与其他骨架系统有着明显的不同,即其下颌体部是通过膜内成骨形成,而下颌支及髁突是通过软骨内成骨形成.下颌运动肌肉的机械牵拉及各种信号分子在下颌发生中发挥着重要作用.     

下颌骨牵引成骨对颞下颌关节的影响

利用牵引成骨技术扩张延长发育不良的下颌骨已获成功,近年来十分盛行。本文综述下颌骨牵引成骨过程对颞下颌关节影响的动物实验和临床应用研究,特别是下颌骨牵引成骨术对下颌骨发育不良病例的髁状突的影响,阐述应用传递牵引技术对重建髁状突切除术的髁状突和颞下颌关节的作用。     

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.     

Identification of temporal pattern of mandibular condylar growth: a molecular and biochemical experiment

OBJECTIVES: Based on the phenomenon that expression of type X collagen and capillary endothelium correlates with endochondral ossification, the prime aim of this study was to establish the temporal pattern of condylar growth in Sprague-Dawley rats by biochemically identifying the expression of these two factors. DESIGN: Sprague-Dawley rats were divided into five groups representing five different stages during somatic pubertal growth. In situ hybridization and immunoperoxidase were performed to examine expression of type X collagen in hypertrophic zone and capillary endothelium in erosive zone of condylar cartilage. Computer-assisted imaging analyses were conducted to allow for a quantitative assessment of the expression of these two factors, from which the temporal pattern of condylar growth was inferred. RESULTS: (1) Synthesis of type X collagen and emergence of capillary endothelium were critical factors during the transition of condylar cartilage from chondrogenesis into osteogenesis, a biological pathway that leads to endochondral bone formation, the mode through which the condyle grows. (2) Quantitative analyses revealed the temporal pattern of the expression of these two factors, indicating that the thrust of natural growth of the condyle in the rats occurred in concomitance with somatic pubertal growth, featured by an acceleration starting from day 38, a maximum growth rate on day 56, followed by a decrease afterwards. CONCLUSION: It is suggested that the biochemical examination of growth markers, such as type X collagen, might be a new approach to accurately depict temporal pattern of condylar growth which is too delicate to be reflected by gross measurement not only in Sprague-Dawley rats but potentially also in other species.     

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.     

A new approach to control condylar growth by regulating angiogenesis

OBJECTIVE: To provide a comprehensive review of the mechanisms of growth of mandibular condyle, the roles of angiogenesis enhancers and inhibitors during endochondral ossification in mandibular condyle and newly developed delivery methods for local gene delivery that may represent strategies to regulate condylar growth. DESIGN: Narrative review. RESULTS: Angiogenesis is the crucial step in mandibular condylar growth for it regulates the transformation from cartilage to bone. Angiognesis enhancers, especially VEGF and FGF, play important roles in the process of new blood lumen formation and invasion. On the other hand, angiostatin and endostatin inhibit angiogenesis by targeting endothelial cells and several signal cascades. Delivery methods such as liposomes, stem cells and virus vectors have been studied. Recombinant AAV-mediated gene therapy is considered as one of the most promising strategies of condylar growth management. CONCLUSION: AAV-mediated gene therapy using VEGF or angiogenesis inhibitor will be a promising way to regulate condylar growth at an early stage.     

PTHrP regulates chondrocyte maturation in condylar cartilage

PTHrP is a key factor regulating the pace of endochondral ossification during skeletal development. Mandibular advancement solicits a cascade of molecular responses in condylar cartilage. However, the pace of cellular maturation and its effects on condylar growth are still unknown. The purpose of this study was to evaluate the pattern of expression of PTHrP and correlate it to cellular dynamics of chondrocytes in condylar cartilage during natural growth and mandibular advancement. We fitted 35-day-old Sprague-Dawley rats with functional appliances. Experimental animals with matched controls were labeled with bromodeoxyuridine 3 days before their death, so that mesenchymal cell differentiation could be traced. Mandibular advancement increased the number of differentiated chondroblasts and subsequently increased the cartilage volume. Higher levels of PTHrP expression in experimental animals coincided with the slowing of chondrocyte hypertrophy. Thus, mandibular advancement promoted mesenchymal cell differentiation and triggered PTHrP expression, which retarded their further maturation to allow for more growth.     

甲状旁腺相关蛋白在鼠胚髁突外植体软骨内成骨中的作用

目的探讨甲状旁腺相关蛋白(PTHrP)对体外培养的鼠胚髁突软骨内成骨的影响。方法体外解剖分离鼠胚髁突,行外植体培养,通过组织学、免疫组化等方法观察PTHrP对体外培养的髁突外植体软骨内成骨的影响。结果髁突外植体在无血清半固态培养系统中能正常发育。加入人PTHrP(1-34)后,实验组髁突长度的增加较对照组明显,两组间差异有显著性(P<0.05);组织学及免疫组化染色显示:加入人PTHrP(1-34)后培养的髁突外植体增殖层和肥大软骨细胞层明显增厚,同时Ⅱ及Ⅹ型胶原在增殖层和肥大软骨细胞层中表达增强。结论PTHrP可刺激髁突外植体软骨增殖层和肥大层软骨细胞的增殖,促进髁突软骨内成骨的形成。?     

Immunohistochemical localization of parathyroid hormone-related protein in developing mouse Meckel''s cartilage and mandible

In order to clarify the role of parathyroid hormone-related protein (PTHrP) during Meckel's cartilage and mandibular development, an immunohistochemical study of PTHrP and its receptor, PTH/PTHrP receptor, was designed to examine their localization in the anterior region of Meckel's cartilage including the rostrum, which is known to contribute to the development of the mandible. Meckel's cartilage was first observed on day 13 of gestation and PTHrP was faintly localized in the chondrocytes. On day 16 of gestation, at the stage of elongation and initiation of endochondral ossificastitial in Meckel's cartilage, PTHrP was localized in the chondrocytes located in the area showing interstitial growth and in and around the nuclei of hypertrophic chondrocytes undergoing endochondral ossification. At day 18 of gestation, endochondral ossification was spread over the entire area proximal to the molar region in Meckel's cartilage, except in the mesial fusion site formed by immature chondrocytes. PTHrP was localized in the osteoblasts adjacent to the calcified matrix, but had disappeared from the chondrocytes forming Meckel's cartilage. The localization of PTH/PTHrP receptor was similar to that of PTHrP. These results show that localization of PTHrP is spatially and temporally related to the growth of Meckel's cartilage.     

Distribution of parathyroid hormone-related protein (PTHrP) and type I parathyroid hormone (PTH) PTHrP receptor in developing mouse mandibular condylar cartilage.

The mandibular condylar cartilage undergoes endochondral bone formation and is an important growth site in the mandible. Parathyroid hormone-related protein (PTHrP) has received attention as a physiological regulator attenuating chondrocytic differentiation and preventing apoptotic cell death. In order to examine the localization of PTHrP and its receptor during fetal development of the condylar cartilage, an immunohistochemical study of PTHrP and the type I PTH/PTHrP receptor was carried out. At day 15 of gestation, the condylar cartilage was evident and some chondrocytes showed positive staining for PTHrP. At day 16, the cartilage was increasing in length and width, and PTHrP was localized in the flattened and hypertrophic cell layers. After day 17, when endochondral bone formation had already started, PTHrP was mainly observed in the flattened cell layer and in a few layers of the hypertrophic chondrocytes. The localization of the type I PTH/PTHrP receptor was similar to that of PTHrP on days 15 and 16, and was broadly distributed at day 18. Apoptotic chondrocytes were scarcely observed on days 15 and 16, and only a few cells were present in the erosion front at day 18. This temporal and spatial localization of PTHrP and the type I PTH/PTHrP receptor suggests that PTHrP is a possible autocrine/ paracrine factor regulating condylar chondrocytic differentiation during development.     

Prenatal developmental process of human temporomandibular joint

The prenatal development of 20 human TMJs from the fourteenth gestational week to full term was studied and the following observations were made. Radiologic findings: at the sixteenth gestational week, the outline of the TMJ as radioopaque structures appeared. Curvature of the articular eminence of the temporal components was observed at gestational week 33, and convexity of the condylar head of the condylar process was observed at the thirty-first week. Histologic findings: at the fifteenth gestational week, thin intramembranous ossification of the temporal components and endochondral ossification of the condylar process were observed, and secondary cartilage occupied the whole condylar process. The articular disk was distinguishable and was composed of fine collagen fibers. At the seventeenth gestational week, endochondral ossification of the condylar process appeared, the formation of joint cavities was fairly completed, and synovial tissues were easily observed. From gestational week 17 through 21, endochondral ossification of the condylar process developed rapidly and the layer structures, which consisted of a fibrous covering layer, transitional cell layer, hypertrophic layer, and erosive layer, were observed. At the twenty-first gestational week, Meckel's cartilage disappeared and hematopoietic foci appeared in the temporal components and the condylar process. Week 21 seemed to be the greatest turning point of the prenatal development of the human TMJ. Secondary cartilage of the condylar process diminished gradually throughout fetal life, but was vestigial at full term.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ⅰ、Ⅱ、Ⅹ型胶原及碱性磷酸酶在鼠胚髁突软骨发生中的意义

目的　探讨髁突软骨发生中Ⅰ、Ⅱ、Ⅹ型胶原及碱性磷酸酶(ALP)的组织学分布特征及髁突软骨内成骨的 分子机制。方法　取14~18 d鼠胚,分别行Ⅰ、Ⅱ、Ⅹ型胶原及ALP抗体免疫组织化学染色。结果　胚胎第14天, 髁突形成的位置可见间充质细胞聚集并与骨膜相连,间充质细胞及骨膜中Ⅰ型胶原及ALP阳性;第15天,肥大软 骨细胞中Ⅹ型胶原表达阳性,其周围的间充质细胞中Ⅰ、Ⅱ型胶原阳性,ALP在两种细胞中均呈阳性;第16天,软骨 膜、纤维层间充质细胞至肥大软骨细胞上层中Ⅰ型胶原表达阳性,多形细胞层下方至肥大软骨细胞下层中Ⅱ型胶 原表达阳性,Ⅹ型胶原仅表达于肥大软骨细胞,ALP在软骨膜及肥大软骨细胞中呈阳性,但在多形细胞层呈阴性或 弱阳性。结论　髁突软骨的发生机制与长骨不同,其软骨内成骨的早期Ⅰ、Ⅱ、Ⅹ型胶原均有表达,可能始发于ALP 阳性的下颌骨膜间充质细胞。