Morphological Changes in the Mandible of Male Mice Associated With Aging and Biomechanical Stimulus

Degenerative changes in the temporomandibular joint (TMJ) associated with aging can affect mandibular shape and reduce growth potential when stimulated by functional appliance therapy. This study was designed to evaluate the morphological changes in the mandibles of male mice associated with aging and biomechanical stimulus. Every 3 days over the course of 1 month, the lower incisors were trimmed by 1 mm to induce mandibular advancement (MA) when the animal was feeding. The left mandibles of the 23 experimental and 27 control animals were subsequently dissected, and digital images were obtained to analyze nine linear/angular measurements. Because mandibular morphology depends on the maintenance of condylar cartilage, the surfaces of the condylar cartilage and the ascending ramus of the mandible were also analyzed by scanning electron microscopy (SEM). The linear measurements of the mandible showed changes according to age in the control group and a growth response in the mandibular condyle in 7‐ and 15‐month‐old mice after MA. Moreover, SEM analysis revealed depressions in the anterior region of the condylar cartilage and inclined vascular grooves in the ascending ramus in the 7‐ and 15‐month‐old experimental mice. Although the growth potential is reduced in mice after 6 months of age, the results showed that continuous growth of the mandible occurs after maturation, except in the condyle, and that biomechanical stimulus of the TMJ of male mice leads to condylar growth. These results suggest that mature and old individuals can favorably respond to maxillary functional orthopedic therapy. Anat Rec, 292:431–438, 2009. © 2009 Wiley‐Liss, Inc.     

Histological analysis of the growth of the mandibular condyle in the rhesus monkey (Macaca mulatta)

Qualitative and quantitative data on the growth of the mandibular condyle in the rhesus monkey (Macaca mulatta) are limited. The purpose of this investigation was to provide such data, with emphasis on variation in the size of the cartilaginous layers in the condyle and on condylar growth at five maturational levels (i.e., neonate, infant, juvenile, adolescent and young adult). Two regions of the mandibular condyle, the articular tissue and the prechondroblastic-chondroblastic (growth) layer, were examined histologically in 38 rhesus monkeys. The absolute area of the articular layer increased dramatically from the neonatal through the juvenile age groups and then decreased gradually through the adult group. When the absolute values were expressed relative to condylar size, the first three maturational levels shared a common trend of increasing growth of the articular layer, with a cessation of growth in this tissue occurring during the adolescent period. This variation in articular layer tissue is probably the result of progressive alteration in the function of the temporomandibular joint. The size of the prechondroblastic-chondroblastic (growth) cartilage increased dramatically between the neonatal and juvenile age groups, and subsequently decreased in older age groups. The relative thickness of the prechondroblastic-chondroblastic cartilage reached its peak within the infant and juvenile levels, being greatest in the posterior region among the infants and in the postero-superior region among the juveniles. This corresponds to previous investigations which have shown that greater vertical growth of the rhesus monkey mandible occurs during the infant period, while the direction of mandibular growth is more horizontal in subsequent age groups.     

颞下颌关节盘前移位对髁状突软骨中纤溶酶原激活剂系统表达的影响

目的研究颞下颌关节盘前移位对关节软骨组织中尿激酶型纤溶酶原激活剂（uPA）系统的影响.方法24只日本大耳白兔在不打开关节囊的情况下建立右侧颞下颌关节盘前移位动物模型,分别于术后4、1、2、4、8d和12周各处死4只动物.常规HE染色观察髁突软骨的形态学变化,并以原位杂交法检测髁突软骨细胞中uPA和纤溶酶原激活剂抑制剂-1（PAI-1）的基因表达变化.结果术后髁突受力区出现一过性的软骨变薄、各层排列紊乱等病理变化.uPA和PAI-1基因转录水平在术后即开始上调,至2周时达到最高水平,至12周时基本恢复至正常水平,与髁突软骨的适应性改建相一致.结论颞下颌关节盘前移位后,关节软骨内uPA系统的变化与关节软骨的适应性改建密切相关.     

In situ hybridisation study of type I, II, X collagens and aggrecan mRNAs in the developing condylar cartilage of fetal mouse mandible

The aim of this study was to investigate the developmental characteristics of the mandibular condyle in sequential phases at the gene level using in situ hybridisation. At d 14.5 of gestation, although no expression of type II collagen mRNA was observed, aggrecan mRNA was detected with type I collagen mRNA in the posterior region of the mesenchymal cell aggregation continuous with the ossifying mandibular bone anlage prior to chondrogenesis. At d 15.0 of gestation, the first cartilaginous tissue appeared at the posterior edge of the ossifying mandibular bone anlage. The primarily formed chondrocytes in the cartilage matrix had already shown the appearance of hypertrophy and expressed types I, II and X collagens and aggrecan mRNAs simultaneously. At d 16.0 of gestation, the condylar cartilage increased in size due to accumulation of hypertrophic chondrocytes characterised by the expression of type X collagen mRNA, whereas the expression of type I collagen mRNA had been reduced in the hypertrophic chondrocytes and was confined to the periosteal osteogenic cells surrounding the cartilaginous tissue. At d 18.0 of gestation before birth, cartilage-characteristic gene expression had been reduced in the chondrocytes of the lower half of the hypertrophic cell layer. The present findings demonstrate that the initial chondrogenesis for the mandibular condyle starts continuous with the posterior edge of the mandibular periosteum and that chondroprogenitor cells for the condylar cartilage rapidly differentiate into hypertrophic chondrocytes. Further, it is indicated that sequential rapid changes and reductions of each mRNA might be closely related to the construction of the temporal mandibular ramus in the fetal stage.     

髁突颈横行截骨和骨折对大鼠下颌骨生长发育的影响

目的 建立年轻SD大鼠单侧髁突颈部截骨、骨折的动物模型,探讨应力改变对大鼠下颌骨及髁突生长发育的影响.方法 4周龄72只雄性SD大鼠按随机数字表法分3组,每组24只,分为截骨组、骨折组、对照组.建立大鼠单侧髁突颈部横行截骨,骨折的动物模型,观察术后1、3、5、9周髁突影像学、组织学及下颌骨解剖学的变化.检测与髁突生长发育关系密切的结缔组织生长因子（CTGF）及X型胶原（Col X）在髁突软骨中表达的变化.结果 截骨组手术侧术后1、3周髁突区膨大,髁突颈呈分离影像.骨折组手术侧术后1周髁突呈圆柱状,见骨折线.截骨组手术侧术后4个时间点下颌骨生长发育受到限制,髁突软骨的总厚度术后1周代偿性增厚为（1468.28±53.73） μm,大于骨折组手术侧;术后3、5周总厚度明显降低;术后9周与骨折组手术侧比较差异无统计学意义（P＞0.05）,但都小于对照组（P＜0.05）.截骨组手术侧CTGF在髁突软骨中的表达在术后1、3、5周分别为60.18±1.23、72.43±2.82、86.00±2.90均高于骨折组手术侧和对照组Col X表达在术后1周时为64.46±3.76,高于骨折组手术侧和对照组（均为P＜0.05）.结论 单侧髁突颈截骨,致应力改变明显,影响下颌骨及髁突生长发育,可导致手术侧、非手术侧下颌骨的不对称,并影响CTGF及Col X在髁突软骨的表达.     

Prenatal development of the human mandible

In an effort to better understand the interrelationship of the growth and development pattern of the mandible and condyle, a sequential growth pattern of human mandibles in 38 embryos and 111 fetuses were examined by serial histological sections and soft X‐ray views. The basic growth pattern of the mandibular body and condyle appeared in week 7 of fertilization. Histologically, the embryonal mandible originated from primary intramembranous ossification in the fibrous mesenchymal tissue around the Meckel cartilage. From this initial ossification, the ramifying trabecular bones developed forward, backward and upward, to form the symphysis, mandibular body, and coronoid process, respectively. We named this initial ossification site of embryonal mandible as the mandibular primary growth center (MdPGC). During week 8 of fertilization, the trabecular bone of the mandibular body grew rapidly to form muscular attachments to the masseter, temporalis, and pterygoid muscles. The mandible was then rapidly separated from the Meckel cartilage and formed a condyle blastema at the posterior end of linear mandibular trabeculae. The condyle blastema, attached to the upper part of pterygoid muscle, grew backward and upward and concurrent endochondral ossification resulted in the formation of the condyle. From week 14 of fertilization, the growth of conical structure of condyle became apparent on histological and radiological examinations. The mandibular body showed a conspicuous radiating trabecular growth pattern centered at the MdPGC, located around the apical area of deciduous first molar. The condyle growth showed characteristic conical structure and abundant hematopoietic tissue in the marrow. The growth of the proximal end of condyle was also approximated to the MdPGC on radiograms. Taken together, we hypothesized that the MdPGC has an important morphogenetic affect for the development of the human mandible, providing a growth center for the trabecular bone of mandibular body and also indicating the initial growth of endochondral ossification of the condyle. Anat Rec 263:314–325, 2001. © 2001 Wiley‐Liss, Inc.     

Mandibular growth retardation in corticosteroid-treated juvenile mice.

Juvenile mice were treated for up to eight weeks with weekly doses of a synthetic analogue of cortisol:triamcinolone hexacetonide. The mandibular condylar cartilage was studied histologically and histochemically at regular intervals. Morphometric measurements were performed along the mandibular posterior vertical dimension (condylar process and ramus). By the second injection significant morphological changes were noted in the condylar cartilage, followed by retardation of bone growth. The most distinctive feature in the cartilage of triamcinolone-treated mice was a marked increase in the dimension of its mineralized zone concomitant with a significant increase in the number of hypertrophic chondrocytes. The role of condylar cartilage in mandibular growth is discussed.     

Mandibular growth retardation in corticosteroid-treated juvenile mice

Juvenile mice were treated for up to eight weeks with weekly doses of a synthetic analogue of cortisol:triamcinolone hexacetonide. The mandibular condylar cartilage was studied histologically and histochemically at regular intervals. Morphometric measurements were performed along the mandibular posterior vertical dimension (condylar process and ramus). By the second injection significant morphological changes were noted in the condylar cartilage, followed by retardation of bone growth. The most distinctive feature in the cartilage of triamcinolone-treated mice was a marked increase in the dimension of its mineralized zone concomitant with a significant increase in the number of hypertrophic chondrocytes. The role of condylar cartilage in mandibular growth is discussed.     

Morphological influence of ascorbic acid deficiency on endochondral ossification in osteogenic disorder Shionogi rat

The influences of chronic deficiency of L-ascorbic acid (AsA) on the differentiation of osteo-chondrogenic cells and the process of endochondral ossification were examined in the mandibular condyle and the tibial epiphysis and metaphysis by using Osteogenic Disorder Shionogi (ODS) rats that bear an inborn deficiency of L-gulonolactone oxidase. Weanling male rats were kept on an AsA-free diet for up to 4 weeks, until the symptoms of scurvy became evident. The tibiae and condylar processes of scorbutic rats displayed undersized and distorted profiles with thin cortical and scanty cancellous bones. In these scorbutic bones, the osteoblasts showed characteristic expanded round profiles of rough endoplasmic reticulum, and lay on the bone surface where the osteoid layer was missing. Trabeculae formation was deadlocked, although calcification of the cartilage matrix proceeded in both types of bone. Scorbutic condylar cartilage showed severe disorganization of cell zones, such as unusual thickening of the calcification zone, whereas the tibial cartilage showed no particular alterations (except for a moderately decreased population of chondrocytes). In condylar cartilage, hypertrophic chondrocytes were encased in a thickened calcification zone, and groups of nonhypertrophic chondrocytes occasionally formed cell nests surrounded by a metachromatic matrix in the hypertrophic cell zone. These results indicate that during endochondral ossification, chronic AsA deficiency depresses osteoblast function and disturbs the differentiation pathway of chondrocytes. The influence of scurvy on mandibular condyle cartilage is different from that on articular and epiphyseal cartilage of the tibia, suggesting that AsA plays different roles in endochondral ossification in the mandibular condyle and long bones.     

Age-related changes in the localization of glycosaminoglycans in condylar cartilage of the mandible in rats

There is little information available regarding the morphological and biomolecular characteristics of mandibular condylar cartilage. The purpose of this study was to determine the age-related changes in the morphology and immunolocalization of glycosaminoglycans (GAGs) in mandibular condyles. The mandibular condylar cartilages from 4-, 8-, 16-, 32-, and 64-week-old Wistar male rats were examined to verify the localization of chondroitin-4-sulfate (Ch-4S), chondroitin-6-sulfate (Ch-6S) and keratan sulfate (KS) using an indirect immunofluorescent technique with three monoclonal antibodies for glycosaminoglycans, 2-B-6, 3-B-3 and 5-D-4, respectively. Morphologically, the condylar cartilage was a growth cartilage during growing periods, began to differentiate into articular cartilage from the central area of 16-week-old condyles, and became mature articular cartilage at 32 weeks of age. A regional difference was found in the morphological features and distribution of GAGs between the anterior, central, postero-superior and posterior areas of the condyles at each age. The immunohistochemical localizations of these three glycosaminoglycans showed age-related, morphology-dependent changes, from growth cartilage to articular cartilage-like cartilage. Immunoreactions for all of the antibodies decreased progressively with age in the interterritorial matrix, while the pericellular and territorial matrix in the condylar cartilage of the mandible maintained relatively higher immunoreactivity. In conclusion, age-related and regional differences in the localization of glycosaminoglycans Ch-4S, Ch-6S, and KS were found in the mandibular condyles in rats, and these changes are believed to be related to functional and developmental requirements.     

Tissue engineering the mandibular condyle

Tissue engineering provides the revolutionary possibility for curing temporomandibular joint (TMJ) disorders. Although characterization of the mandibular condyle has been extensively studied, tissue engineering of the mandibular condyle is still in an inchoate stage. The purpose of this review is to provide a summary of advances relevant to tissue engineering of mandibular cartilage and bone, and to serve as a reference for future research in this field. A concise anatomical overview of the mandibular condyle is provided, and the structure and function of the mandibular condyle are reviewed, including the cell types, extracellular matrix (ECM) composition, and biomechanical properties. Collagens and proteoglycans are distributed heterogeneously (topographically and zonally). The complexity of collagen types (including types I, II, III, and X) and cell types (including fibroblast-like cells, mesenchymal cells, and differentiated chondrocytes) indicates that mandibular cartilage is an intermediate between fibrocartilage and hyaline cartilage. The fibrocartilaginous fibrous zone at the surface is separated from hyaline-like mature and hypertrophic zones below by a thin and highly cellular proliferative zone. Mechanically, the mandibular condylar cartilage is anisotropic under tension (stiffer anteroposteriorly) and heterogeneous under compression (anterior region stiffer than posterior). Tissue engineering of mandibular condylar cartilage and bone is reviewed, consisting of cell culture, growth factors, scaffolds, and bioreactors. Ideal engineered constructs for mandibular condyle regeneration must involve two distinct yet integrated stratified layers in a single osteochondral construct to meet the different demands for the regeneration of cartilage and bone tissues. We conclude this review with a brief discussion of tissue engineering strategies, along with future directions for tissue engineering the mandibular condyle.     

The effect of dietary consistency on gross and histologic morphology in the craniofacial region of young rats

Three groups of weanling rats and three groups of juvenile rats were fed diets which differed in physical consistency for periods of 5 and 8 weeks, respectively. In both the weanling and juvenile rats, one group was fed a soft diet, a second group was fed a hard diet, and a third group was initially fed the soft diet and then was switched to the hard diet for the remainder of the experimental period. The effects of these differences in dietary consistency on gross and histologic morphology of the craniofacial region were examined. Significant differences were found in the dimensions and morphology of the condyle and condylar cartilage as a result of the differences in dietary consistency in both the weanling and juvenile groups. Soft-diet rats generally had smaller condyles and a thinner layer of condylar cartilage than either hard-diet or soft/hard-diet rats. Little change, however, was found in the overall dimensions of the mandible and maxilla in any of the groups of rats.     

Regenerative Potential of Mandibular Condyle Cartilage and Bone Cells Compared to Costal Cartilage Cells When Seeded in Novel Gelatin Based Hydrogels

The field of temporomandibular joint (TMJ) condyle regeneration is hampered by a limited understanding of the phenotype and regeneration potential of cells in mandibular condyle cartilage. It has been shown that chondrocytes derived from hyaline and costal cartilage exhibit a greater chondro-regenerative potential in vitro than those from mandibular condylar cartilage. However, our recent in vivo studies suggest that mandibular condyle cartilage cells do have the potential for cartilage regeneration in osteochondral defects, but that bone regeneration is inadequate. The objective of this study was to determine the regeneration potential of cartilage and bone cells from goat mandibular condyles in two different photocrosslinkable hydrogel systems, PGH and methacrylated gelatin, compared to the well-studied costal chondrocytes. PGH is composed of methacrylated poly(ethylene glycol), gelatin, and heparin. Histology, biochemistry and unconfined compression testing was performed after 4 weeks of culture. For bone derived cells, histology showed that PGH inhibited mineralization, while gelatin supported it. For chondrocytes, costal chondrocytes had robust glycosaminoglycan (GAG) deposition in both PGH and gelatin, and compression properties on par with native condylar cartilage in gelatin. However, they showed signs of hypertrophy in gelatin but not PGH. Conversely, mandibular condyle cartilage chondrocytes only had high GAG deposition in gelatin but not in PGH. These appeared to remain dormant in PGH. These results show that mandibular condyle cartilage cells do have innate regeneration potential but that they are more sensitive to hydrogel material than costal cartilage cells.

     

Remarks on the morphology of the human temporomandibular joint in the fetal period

Skeletons of human fetuses of different ages allow the study of the considerable transformations of the mandibular joint and the mandible in this relative short stage of life. The condyle is anchored in the mandible by a conical process. The tip of this cone extends to the anLage of the 2nd milk molar. The conical process can be recognized macroscopically up to newborn age. It can also be identified by modern imaging methods. The cone can be well distinguished from the surrounding bone of the mandible. The mandibular joints of fetuses in the 31st, the 32nd, the 39th week and of a newborn were dissected, removed, and histologically investigated. The conical process of the condyle was clearly observed. The cartilage on the condyle is characterised by a layered structure which is typical for a center of growth. In the cartilage of young fetuses, blood vessels were found, reaching from the trabecular bone to the articular space. At this stage of life, blood vessels are also present in the central part of the discus articularis.     

Effects of condylar fibrocartilage on the biomechanical loading of the human temporomandibular joint in a three-dimensional,nonlinear finite element model

The present study was undertaken to test a hypothesis that the addition of articular fibrocartilage in the condyle of the temporomandibular joint reduces three-dimensional stress distribution in the condyle, the disc and articular eminence. A three-dimensional, nonlinear finite-element model was developed for analysis of joint loading before and after the addition of condylar fibrocartilage to the osseous mandibular condyle reconstructed from spiral computer topography data. In the model, each of the disc, condyle and articular eminence was arbitrarily divided into five regions: the anterior, posterior, medial, lateral and central. Von Mises stresses that in virtually all regions of the disc, condyle and articular eminence became lower after the addition of condylar fibrocartilage. Especially remarkable was the approximately four-fold reduction in von Mises stresses in the anterior, central and medial regions of the mandibular condyle. In comparison, only slight to moderate stress reductions occurred in the disc and articular eminence, suggesting that condylar fibrocartilage absorbs considerable stresses and likely dampens more loads than the disc and articular eminence. The mandibular condyle demonstrated the largest total displacement in all directions after the addition of articular fibrocartilage, followed by the disc and articular eminence. We conclude that the addition of articular fibrocartilage primarily reduces loading of the mandibular condyle, rather than the disc and articular eminence. These findings lead to a hypothesis that the mandibular condyle more likely functions as a shock absorber than the disc.     

成人下颌孔及周边骨性结构的解剖特点

目的:研究成人下颌孔及周边骨性结构的解剖特点,为临床手术操作提供解剖参考和依据.方法:由口腔专业教师确定各解剖结构的位置并标记,用游标卡尺、量角器、直尺和圆规对下颌骨进行测量,记录数据并进行统计学分析.结果:有76.00％的下颌孔位于下颌支内面中点之后,有87.00％的下颌孔位于下颌支内面中点之上;下颌孔的内外径为3....     

Magnetic resonance imaging findings of true bifid mandibular condyle with duplicated mandibular fossa

Bifid mandibular condyle (BMC) is a rare asymptomatic morphological alteration with no predilection for age group or gender. Its morphology varies from a shallow groove to two condylar heads with separate necks, oriented mediolaterally or anteroposteriorly. This report describes an unusual case of anteroposterior bifid condyle in a 39-year-old female patient with the main complaint of mouth-opening limitation and a deviation of the mandible to the left side. Magnetic resonance imaging (MRI) findings revealed a bifid condyle on the left side and duplicated mandibular fossa, with the articular disc over the anterior head. The MRI images in the open-mouth position revealed minimal movement of the condyle. Despite the increased number of mediolateral bifid mandibular condyle cases described in the literature, none of previously reported cases of BMC included an anteroposterior bifid condyle case with two distinct mandibular fossa.     

人髁突软骨组织各带厚度的测量

用连续切片，多点测量法对４３例１９－７４岁人髁突软骨各带厚度进行了测量。结果显示：髁突软骨各带厚度不恒定，波动起伏较大。肥大带厚度在前斜面，横嵴与后斜面存在显著性差异。增殖带厚度在青年组与壮年。料老年组间存在有显著性差异，但壮年组与老年组则无显著性差异，而各区厚度与年龄呈负相关关系。     

Histological changes in the articular eminence and mandibular fossa during growth of the rhesus monkey (Macaca mulatta)

Unlike the mandibular condyle, the temporal component of the temporomandibular joint (TMJ) has been the object of relatively few investigations concerning its growth and remodeling. This report provides qualitative and quantitative documentation of microanatomical changes in the mandibular fossa and articular eminence during growth of the rhesus monkey (Macaca mulatta). The thickness of the fibrous articular tissue and the presence of cartilage cells in its deeper layers were examined histologically in 43 rhesus monkeys at five maturational levels (neonate, infant, juvenile, adolescent, and young adult). Absolute thickness of the articular tissue increased with maturational level in all areas studied, with the increase somewhat more pronounced on the posterior slope and crest of the articular eminence than in the roof of the mandibular fossa. Relative to condylar size, an increase in articularlayer thickness characterized the first three maturational levels, and was followed by a decrease during adolescent and young-adult stages. Articular tissue in the fossa roof constituted a steadily decreasing fraction of the total articular-tissue thickness with age, while relative thickness of the tissue on the posterior slope and crest of the eminence increased with age. These results parallel those obtained for the mandibular condyle, and they are best interpreted to indicate that forces delivered to the joint become directed more anteriorly with age. The overall pattern of topographical variation in articular-tissue thickness and cartilage-cell distribution suggests that greater loading of the lateral aspect of the TMJ, postulated in the human TMJ by various workers, may not be as pronounced in the monkey.     

下颌骨缺损腓骨瓣修复不同固定方式的有限元分析

背景:肿瘤、外伤等原因常常造成下颌骨节段性缺损,血管化腓骨瓣同期重建下颌骨缺损是目前最主要的修复方式。目前在临床上既有用重建钛板进行固定,又有用小型钛板固定,有临床回顾性研究表明重建钛板和小型钛板固定方式患者术后并发症率无明显差异,但目前仍缺少固定稳定性相关的生物力学研究。目的:试验用三维有限元法分析下颌骨节段性缺损腓骨瓣修复时用重建钛板和小型钛板固定后的应力分布和稳定性。方法:选择1例牙列完整的成年男性进行CT扫描,并将数据录入计算机之后重建下颌骨及牙列模型,根据下颌骨缺损的Jewer分类,建立H(一侧下颌体、下颌角、下颌升支和髁突的缺失),L(一侧下颌体缺失)和C(双侧下颌骨颏部缺失)3类缺损三维模型,利用三维有限元分析法,对这3种下颌骨缺损腓骨修复后重建板和小型板固定的力学分布特点和稳定性进行对比研究。结果与结论:①从应力云图可以大致判断,正常下颌骨应力较大值主要发生在髁突、髁颈、下颌角、磨牙、钛板钛钉等周围区域处,尤其以下颌角附近处应力最大;②H类缺损在重建钛板修复下颌骨时将对下颌角附近产生较大应力,局部应力集中达185MPa,在H类小型钛板、L类小型钛板及重建钛板修复条件下,钛板的应力为117-135 MPa,腓骨块的应力最大值基本在30.4 MPa以下,钛钉应力最大值为56.2 MPa;③H及L类缺损小型钛板、重建钛板修复后骨断端相对位移变化为15-18μm,C类缺损下颌骨钛板修复后骨断端基本不产生相对位移;④结果证实,重建钛板和小型钛板均能满足这3种缺损腓骨修复的生物力学要求。