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.     

Histological and histomorphometric investigation of the condylar cartilage of juvenile pigs after anterior mandibular displacement

The condylar cartilage of the mandible is considered a secondary growth center and represents a joint cartilage different from other cartilage structures regarding its histological structure, its histochemical and immunohistochemical properties and its growth pattern. This study aimed to histologically and histomorphometrically investigate the condylar cartilage after anterior mandibular displacement similar to functional orthopedic treatment. A total of 12 pigs (sus scrofa domesticus) aged 10 weeks were divided into an experimental group and a control group comprising 6 animals each. The experimental animals were provided bilaterally with synthetic occlusal build-ups in the posterior area which induced anterior displacement of the mandible in terminal occlusion. After 4 weeks, the temporomandibular structures were removed en bloc and the condylar cartilage was analyzed histologically and histomorphometrically. As a result, the experimental animals displayed a significantly increased total cartilage thickness of the posterocranial mandibular condyle which was primarily caused by an increase in thickness of the hypertrophic and chondogenic layers. Similarly, the proliferative layer showed a significant increase, whereas significant differences in thickness were absent in the articular layer. Increased cell proliferation was not observed in the experimental animals as compared to the controls. The changes found in the condylar cartilage area suggest that the zonal structure of the condylar cartilage may be modified by an altered spatial relationship between the mandibular condyle and the glenoid fossa.     

Unilateral masticatory function changes the proteoglycan content of mandibular condylar cartilage in rabbit

Unilateral masticatory function was induced in 10-day-old rabbits by grinding the right side molars out of occlusion under general anesthesia. The grinding procedure was repeated twice a week thereafter. They were killed at the ages of 25 and 35 days. Rabbits of the same age with uninterfered occlusions served as controls. The changes in articular cartilage of the mandibular condyle were studied biochemically and histochemically. There was a significant decrease in the proteoglycan content of the condylar cartilage in both groups of animals subjected to molar grinding compared to the animals with untouched occlusions. Especially the amount of aggregating proteoglycans was reduced. The condylar cartilage matrix synthesis is sensitive to loading produced by masticatory function during growth. The mechanical properties of the articular cartilage after a period of unilateral mastication will be impaired and it is possible that this makes the joint cartilage more susceptible to pathological events.     

Localization of types I, II and III collagen and glycosaminoglycans in the mandibular condyle of growing monkeys: an immunohistochemical study

 In order to analyse the regional and age-related variations of primate condyles, immunohistochemical techniques were used to examine the localization of types I, II and III collagen and a variety of glycosaminoglycans in distinct anteroposterior regions of the mandibular condyle of two growing female rhesus monkeys (Macaca mulatta). In the juvenile monkey staining for types I and III collagen was weak in the fibrous tissue layer, intense in the pre-cartilaginous tissue layer and faint in the cartilaginous tissue layer; staining was significantly more intense in the posterosuperior and posterior regions than in the anterior region. Similarly, staining for cartilage-characteristic extracellular matrices, including type II collagen and keratan sulfate, was intense in the cartilaginous tissue layer of the posterior condyle. In contrast, in the late-adolescent monkey staining for the extracellular matrices was more intense in the anterior half of the condyle (i.e. from the anterior to the posterosuperior region) than in the posterior region, and most intense in the posterosuperior region. The results demonstrate that marked regional differences exist in the phenotypic expression of the extracellular matrices in the mandibular condyles of growing monkeys and that these differences vary between different developmental stages. The variations probably reflect the predominance of competing growth and articulatory functions in the mandibular condyles. Accepted: 19 July 1996     

Age changes in the articular tissue of human mandibular condyles from adolescence to old age: A semiquantitative light microscopic study

In a previous study (Luder, Anat. Rec., 1997;248:18–28), the articular tissue of the adult mandibular condyle was characterized semiquantitatively. However, questions about age changes of mature tissue were not answered, and the time course of tissue maturation from the end of condylar growth to the attainment of the adult appearance remained unknown. These issues are addressed in the present investigation. By using a light microscope, features of the superficial, intermediate, and deep articular tissue zones as well as of the subchondral bone were assessed at nine predetermined condylar sites. The frequencies of these features were recorded as scores from 0 (absent) to 10 (continuous) and were plotted against age. Analysis of covariance served for testing the significance of age and sex effects as well as intracondylar variability. Whereas almost all age-related changes in frequencies of tissue features were similar along the whole lateromedial dimension, changes at the putatively nonload-bearing, posterior slope differed significantly from those at the putatively load-bearing, anterior slope and zenith of the condyle. Two patterns of changes were noted. Frequencies of a first group of tissue features altered mainly during the age period from 15 years to 30 years and remained more or less stable thereafter. This course was characteristic for 1) a progressive cartilaginification of the superficial zone as well as 2) the disappearance of hypertrophic growth cartilage and 3) the appearance of grid-fibrous fibrocartilage in the deep zone, which were accompanied by 4) a decline in endochondral ossification and 5) the formation of a compact, subchondral bone plate. Frequencies of a second group of tissue features disclosed changes that continued up to middle and old age. This pattern was evident regarding 1) a decrease in the prominence associated with 2) a drop in cellularity and 3) progressive fibrosis or even cartilaginification of the intermediate zone. Among the age changes of condylar articular tissue, those affecting the superficial and deep zones as well as the subchondral bone are largely complete by about 30 years of age and seem to be related primarily to a gradual transition from growth to adulthood. In contrast, a second group of alterations, which progress to old age and involve mainly the intermediate zone, appears to be associated with continued maintenance and adaptive articular remodeling as well as possibly senescence. Both maturational and later age changes seem to depend markedly on articular load bearing. Anat. Rec. 251:439–447, 1998. © 1998 Wiley-Liss, Inc.     

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.     

Light and electron microscopic morphology of the temporomandibular joint in growing and mature crab-eating monkeys (Macaca fascicularis): the condylar calcified cartilage.

Summary In an attempt to show maturational alterations in the calcified cartilage, mandibular condyles of four growing and four adult male monkeys (Macaca fascicularis) were studied using light microscopy as well as transmission and scanning electron microscopy. All specimens were initially fixed by perfusion in the presence of ruthenium red. For examination of the hard tissue surfaces in the scanning electron microscope, uncalcified tissues were removed with sodium hypochlorite. In growing animals, almost the entire hard tissue surface in the joint region of the condyle was formed by calcified cartilage, while in adult animals, calcified cartilage was confined to load-bearing regions. In growing animals, the appearance of the calcified cartilage surface suggested a continuously advancing mineralizing front similar to that seen in the epiphyseal plate. Chondrocytes mostly exhibited a terminal stage of hypertrophy, and seemed to die and get lost through vascular invasion and subsequent endochondral ossification. In adult animals, most of the calcified cartilage surface appeared comparatively stable, and resembled the tidemark of articular cartilage. Chondrocytes were usually small and appeared viable. However, on the adult condyles, there were always circumscribed islands where chondrocytes and the pattern of mineralization resembled those seen in growing animals. In these regions, prominent chondroclastic activity indicated extensive articular remodelling. These observations suggest that at the end of somatic growth, condylar calcified cartilage undergoes considerable maturation from a type reminiscent of hyaline growth cartilage to a type resembling articular cartilage. Concomitantly, chondrocytes appear to change their developmental program, in that they stop enlarging and lose their commitment to death. However, they may be able to retain, or switch back to, a more immature stage, in case there is need for extensive articular remodelling.     

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.     

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.     

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.     

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.     

Light and electron microscopic morphology of the temporomandibular joint in growing and mature crab-eating monkeys (Macaca fascicularis): the condylar articular layer

In an attempt to establish maturational alterations in the morphology of the articular tissue layer, mandibular condyles of four immature and four mature male monkeys (Macaca fascicularis) were studied using light microscopy as well as scanning and transmission electron microscopy. Specimens were fixed in situ by perfusion in the presence of ruthenium red to stabilize proteoglycans. Preparations intended for observation in the scanning electron microscope were first dehydrated and sputtered for the examination of articular surfaces, and afterwards treated with trypsin to expose the spatial arrangement of collagen fibrils. Gross anatomical relations between joint components indicated that the anterior and central, but not the posterior region of the condylar articular surface can be subject to compressional load. Load-bearing and non-load-bearing regions differed with respect to the morphology of the articular layer. Load-bearing surfaces were covered by a prominent articular surface lamina similar to that observed on articular cartilage. This lamina seemed to constitute an integral part of the articular layer, distinct from the lining of synovial fluid, and to be composed largely of proteoglycans. It was unaffected by maturation. The subjacent, load-bearing articular layer differed markedly in structure, both from articular cartilage, and between immature and mature animals. Articular cells of immature animals were classified as fibroblastlike, but unlike typical fibroblasts, were surrounded by a thin, often incomplete halo of fibril-free pericellular matrix, presumably consisting of proteoglycans. In mature animals, articular cells closely resembled chondrocytes, but exhibited prominent nuclear fibrous laminae, which usually are found only in fibroblasts. Thus, the load-bearing part of the articular layer seems to undergo a maturation-dependent metaplastic conversion, from a dense connective tissue with some features of fibrocartilage, to a fibrocartilage-like tissue containing chondrocyte-like cells with some features of fibroblasts. This conversion might reflect an adaptation to a maturation-associated increase in articular stress.     

Aggregation of proteoglycans in cephalic, epiphyseal and articular cartilages in growing sheep

The purpose of this study was to determine whether there are age and site related differences in proteoglycan aggregation in craniofacial and epiphyseal cartilages from neonatal and two-month-old lambs. Proteoglycans were extracted using a dissociative extraction method, and aggregates and monomers separated with molecular sieving. Only a small proportion of the proteoglycans were isolated as aggregates in the articular and mandibular condylar cartilage of the neonatal animals, while in the nasal septal, epiphyseal and synchondrosal cartilages of the same animals the portion of proteoglycans isolated as aggregates, was 3 to 6 times as high. During the first 2 months of postnatal development the proportion of proteoglycans isolated as aggregates tripled in the articular and mandibular condylar cartilages, it decreased substantially in the anterior and posterior nasal septum, while it decreased slightly in the other cartilages. These observations indicate that there are age and site related differences in the extent of proteoglycans isolated as aggregates in cephalic, epiphyseal and articular cartilages.     

Age-dependent physiological changes in the histoarchitecture of the articular cartilage of the rabbit mandibular condyle: a morphological and morphometric study

Mandibular condyle articular cartilage participates in condylar postnatal growth and is responsible for adaptations to anatomical and/or biomechanical alterations throughout life. In a preliminary study in rabbits, differences were observed in the thickness of the layers of articular cartilage in control animals at 5 and 6 months (generally considered adults for this purpose). This study aimed to describe sagittally sectioned condylar cartilages stained with Picrosirius-hematoxylin in rabbits at 40 days and 5, 6, 8, 13, and 18 months to determine when histological maturity is reached. At 40 days, 5 layers were seen: fibrous, proliferative, transition, maturation, and hypertrophic. Older animals (5-18 months) lacked the transition layer. Fibrous, proliferative, and hypertrophic regions were considered for morphometric analysis. The thickness of the fibrous region did not change during the analyzed period (p = 0.1899). When proliferative and hypertrophic regions and the total thickness of the cartilage were compared, a difference was detected (p < 0.001). The thickness of the proliferative region was greatest at 40 days and decreased at 5 months; however, it increased at 6 months, when it was significantly thicker than at 5, 8, 13, and 18 months. Both the hypertrophic region and the total thickness were thickest at 40 days, intermediate at 5, 6, and 8 months, and thinnest at 13 and 18 months. In summary, our data suggest a physiological period of increased cartilage growth at 6 months. Additionally, rabbits at this age should be avoided in experiments involving condylar cartilage. Finally, 13-month-old rabbits have reached histological maturity of the condylar cartilage.     

Mechanical stimulation of TMJ condylar chondrocytes encapsulated in PEG hydrogels

Temporomandibular joint (TMJ) disorders are most commonly associated with TMJ disc dislocation and osteoarthritis, which can cause erosion of the articular cartilage on the head of the mandibular condyle. There has been little attention focused on treating the damaged condylar cartilage. Therefore, the overall goal of this research is to create a tissue engineering therapy for resurfacing the damaged cartilage of the condylar process with healthy living tissue. Initially, bovine condylar cartilage explants were studied to understand the tissue structure, composition, and gene expression of the native tissue. The cell response of isolated condylar chondrocytes encapsulated in photopolymerized poly(ethylene glycol) hydrogels as a tissue engineering scaffold was examined in the presence and absence of dynamic loading for up to three days of culture. Condylar chondrocyte viability was maintained within the PEG hydrogel constructs over the culture period and loading conditions. Cell response was examined through real-time RTPCR for collagen types I and II and aggrecan, nitric oxide production, cell proliferation, proteoglycan (PG) synthesis, and spatial distribution of extracellular matrix through histology. This study demonstrates that PEG hydrogel constructs are suitable for condylar chondrocyte encapsulation in the absence of loading. However, dynamic compressive strains resulted in inhibition of gene expression, cell proliferation, and PG synthesis.     

On the development, morphology and function of the temporomandibular joint in the light of the orofacial system.

The temporomandibular joint has a key role in the biocybernetic functional cycle of the orofacial system. It has developed as a "secondary joint" and displays a number of features relating to the articular tubercle, the mandibular condyle, the articular disc, the joint cartilage and the retroarticular pad. The joint cartilage of the mandibular condyle is a primary compensatory growth centre also comprising distant effects. The coordinate course of the mandibular movements is controlled by a complex reflex mechanism and neuronal controller cycles. Morphology, function and clinical aspects are of equal interest to both physicians and dentists.     

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.     

Differential responses to parathyroid hormone‐related protein (PTHrP) deficiency in the various craniofacial cartilages

PTHrP null mutant mice exhibit skeletal abnormalities both in the craniofacial region and limbs. In the growth plate cartilage of the null mutant, a diminished number of proliferating chondrocytes and accelerated chondrocytic differentiation are observed. In order to examine the effect of PTHrP deficiency on the craniofacial morphology and highlight the differential feature of the composing cartilages, we examined the various cartilages in the craniofacial region of neonatal PTHrP deficient mice. The major part of the cartilaginous anterior cranial base appeared to be normal in the homozygous PTHrP deficient mice. However, acceleration of chondrocytic differentiation and endochondral bone formation was observed in the posterior part of the anterior cranial base and in the cranial base synchondroses. Ectopic bone formation was observed in the soft tissue‐running mid‐portion of the Meckel's cartilage, where the cartilage degenerates and converts to ligament in the course of normal development. The zonal structure of the mandibular condylar cartilage was scarcely affected, but the whole condyle was reduced in size. These results suggest the effect of PTHrP deficiency varies widely between the craniofacial cartilages, according to the differential features of each cartilage. Anat Rec 255:452–457, 1999. © 1999 Wiley‐Liss, Inc.