Histochemical and Ultrastructural Study of Developing Gonial Bone With Reference to Initial Ossification of the Malleus and Reduction of Meckel's Cartilage in Mice

Development of mouse gonial bone and initial ossification process of malleus were investigated. Before the formation of the gonial bone, the osteogenic area expressing alkaline phosphatase and Runx2 mRNA was widely recognized inferior to Meckel's cartilage. The gonial bone was first formed within the perichondrium at E16.0 via intramembranous ossification, surrounded the lower part of Meckel's cartilage, and then continued to extend anteriorly and medially until postnatal day (P) 3.0. At P0, multinucleated chondroclasts started to resorb the mineralized cartilage matrix with ruffled borders at the initial ossification site of the malleus (most posterior part of Meckel's cartilage). Almost all CD31-positive capillaries did not run through the gonial bone but entered the cartilage through the site where the gonial bone was not attached, indicating the forms of the initial ossification site of the malleus are similar to those at the secondary ossification center rather than the primary ossification center in the long bone. Then, the reducing process of the posterior part of Meckel's cartilage with extending gonial bone was investigated. Numerous tartrate-resistant acid phosphatase-positive mononuclear cells invaded the reducing Meckel's cartilage, and the continuity between the malleus and Meckel's cartilage was completely lost by P3.5. Both the cartilage matrix and the perichondrium were degraded, and they seemed to be incorporated into the periosteum of the gonial bone. The tensor tympani and tensor veli palatini muscles were attached to the ligament extending from the gonial bone. These findings indicated that the gonial bone has multiple functions and plays important roles in cranial formation. Anat Rec, 302:1916–1933, 2019. © 2019 American Association for Anatomy     

Lack of association between avian cartilages of different embryological origins when maintained in vitro

The possibility that cartilages of differing embryological origins behave as separate types with respect to cell-to-cell associations was tested by placing the cut ends of transversely sectioned embryonic chick tibial cartilages (of mesodermal origin) in apposition to transversely sectioned Meckel's cartilages (a neural crest (ectodermal) cartilage) on the surface of a semi-solid organ culture medium and maintaining the combinations in vitro for five to ten days. Tibia-tibia and Meckel's cartilage-Meckel's cartilage (homotypic) combinations, which served as controls, became united by a common extracellular matrix and by the proliferation of chondroblasts. Analysis of combinations where one partner had been prelabelled with ³H-thymidine indicated that chondroblasts intermingled at the contact zone. In contrast, tibia-Meckel's cartilage (heterotypic) combinations became separated by a layer of fibrous tissue. The chondroblasts at the contact zone failed to intermingle. We conclude that avian embryonic chondrocytes are not all equivalent and that part of their non-equivalence could be related to their embryological origin either from the mesoderm or from the ectodermal neural crest.     

Differential changes in cartilage cell proliferation and cell density in the rat craniofacial complex during secondary palate development

During mammalian secondary palate formation sagittal growth of the lower face has been shown to be more rapid than that of the upper face, and the tongue and mandible extend beneath the primary palate. In order to identify factors contributing to this differential growth pattern, cellular and morphologic growth of the major cartilages of the upper and lower facial regions were studied in radioautographic sections labeled with tritiated thymidine. Evaluation of cell-density recordings, labeling indices, and structural dimensions revealed significant differences between Meckel's cartilage in the lower face, and the nasal cartilage and anterior cranial base cartilage in the upper face. After formation of the precartilaginous blastema, labeling indices were high in Meckel's cartilage (20–30%), but very low in the nasal cartilage and the anterior cranial base (0–2%). During secondary palate formation of the volume of Meckel's cartilage increased more rapidly than the other cartilages and its growth was primarily in the sagittal direction. Between days 15 and 17, the increase in the length of Meckel's cartilage (165%) was approximately twice as great as the increase in the combined length of the nasal cartilage and the anterior cranial base (77%). During this period induction of cleft palate with some teratogens has been shown to severely retard growth of Meckel's cartilage and produce mandibular retrognathia that contributes to delayed elevation of the palatal shelves. Therefore, extensive cell proliferation in Meckel's cartilage, during a period of limited proliferation in other craniofacial cartilages, appears to contribute to its rapid growth and its differential sensitivity to growth inhibition.     

A morphometric analysis of craniofacial growth and changes in spatial relations during secondary palatal development in human embryos and fetuses

Staged human embryos and fetuses in the Carnegie Embryological Collection were morphometrically analyzed to show craniofacial dimensions and changes in spatial relations, and to identify patterns that would reflect normal developmental events during palatal formation. Normal embryos aged 7–8 weeks postconception (Streeter-O'Rahilly stages 19–23) and fetuses aged 9–10 weeks postconception, in eight groups with mean crownrump (CR) lengths of 18–49 mm, were studied with cephalometric methods developed for histologic sections. In the 4-week period studied, facial dimensions increased predominantly in the sagittal plane with extensive changes in length (depth) and height, but limited changes in width. Growth of the mandible was more rapid than the nasomaxillary complex, and the length of Meckel's cartilage exceeded the length of the oronasal cavity at the time of horizontal movement of the shelves during stage 23. Simultaneously with shelf elevation, the upper craniofacial complex lifted, and the tongue and Meckel's cartilage extended forward beneath the primary palate. Analysis of spatial relations in the oronasal cavity showed that the palatomaxillary processes became separated from the tongue-mandibular complex as the head extended, and the tongue became positioned forward with growth of Meckel's cartilage. As the head position extended by 35°, the cranial base angulation was unchanged and the primary palate maintained a 90° position to the posterior cranial base. However, the sagittal position of the maxilla relative to the anterior cranial base increased by 20° between stages 19 and 23. In the late embryonic and early fetal periods, the mean cranial 128° and the mean maxillary position angulation of approximately 34° were similar to the angulations previously shown to be present later prenatally and postnatally. The results suggest that human patterns of cranial base angulation and maxillary position to the cranial base develop during the late embryonic period when the chondrocranium and Meckel's cartilage form the primary skeleton.     

Distribution of Matrix Proteins in Perichondrium and Periosteum During the Incorporation of Meckel's Cartilage into Ossifying Mandible in Midterm Human Fetuses: An Immunohistochemical Study

Immunohistochemical localization of versican and tenascin‐C were performed; the periosteum of ossifying mandible and the perichondrium of Meckel's cartilage, of vertebral cartilage, and of mandibular condylar cartilage were examined in midterm human fetuses. Versican immunoreactivity was restricted and evident only in perichondrium of Meckel's cartilage and vertebral cartilage; conversely, tenascin‐C immunoreactivity was only evident in periosteum. Therefore, versican and tenascin‐C can be used as molecular markers for human fetal perichondrium and fetal periosteum, respectively. Meckel's cartilage underwent endochondral ossification when it was incorporated into the ossifying mandible at the deciduous lateral incisor region. Versican immunoreactivity in the perichondrium gradually became weak toward the anterior primary bone marrow. Tenascin‐C immunoreactivity in the primary bone marrow was also weak, but tenascin‐C positive areas did not overlap with versican‐positive areas; therefore, degradation of the perichondrium probably progressed slowly. Meanwhile, versican‐positive perichondrium and tenascin‐C‐positive periosteum around the bone collar in vertebral cartilage were clearly discriminated. Therefore, the degradation of Meckel's cartilage perichondrium during endochondral ossification occurred at a different rate than did degradation of vertebral cartilage perichondrium. Additionally, the perichondrium of mandibular condylar cartilage showed tenascin‐C immunoreactivity, but not versican immunoreactivity. That perichondrium of mandibular condylar cartilage has immunoreactivity characteristic of other periosteum tissues may indicate that this cartilage is actually distinct from primary cartilage and representative of secondary cartilage. Anat Rec, 297:1208–1217, 2014. © 2014 Wiley Periodicals, Inc.     

Origin of the torus mandibularis: An embryological hypothesis

Torus mandibularis, a well‐known protuberance in the dental field, has been defined as a hyperostosis in the lingual aspect of the body of the mandible above the mylohyoid line. However, the origin of the torus mandibularis has not yet been clarified. The aim of this study was to provide a better understanding on the origin of the torus in view of the specific development of Meckel's cartilage at the site corresponding to the adult torus. A total of 40 mid‐term human fetuses at 7–16 weeks of gestation were examined. The 10–13 weeks stage corresponded to the critical period in which Meckel's cartilage with endochondral ossification underwent a bending at the beginning of the intramandibular course. At the level of mental foramen, which was located between the deciduous canine and the first deciduous molar germs, the medial lamina of the mandible protruded medially to reach Meckel's cartilage. Thus, the medial lamina covered the posterior and superior aspect of the bending Meckel's cartilage just above the attachment of the developing mylohyoid muscle (i.e., in the oral cavity). We considered a bony prominence, which composed the protruding medial lamina and the bending Meckel's cartilage as the fetal origin of the torus mandibularis. A new theory is proposed for the origin of the torus mandibularis based on the existence of an anlage formed during the development of the mandible, variable in morphology and size, but always constant. Clin. Anat. 26:944–952, 2013. © 2013 Wiley Periodicals, Inc.     

Transmission and scanning electron microscope studies of calcified cartilage resorption

The authors' previous report (Savostin-Asling and Asling, 1973) demonstrated that Meckel's cartilage is a favorable site for study of calcified cartilage resorption. In the present study the ultrastructural features at this resorption front have been examined by transmission and scanning electron microscopes (19-day rat fetus). Multinucleated giant cells (chondroclasts) dominated the erosion front. The many features which they showed in common with osteoclasts included abundant mitochondria, vacuolation, lysosomes, sparsity of roughsurfaced endoplasmic reticulum, and deep infoldings at loci of contact with calcified matrix. Crumbling of matrix (with mineral crystals penetrating between these foldings) and fragmentation of collagen fibrils were also seen. The propensity of chondroclasts for spanning several opened lacunae provided special opportunity to demonstrate cell surface modifications in presence or absence of matrix contact. Ameboid processes extending into lacunae were seen by both transmission and scanning procedures; they were sometimes tipped with a veil of filamentous processes as small as 0.3 μm in diameter. Most hypertrophic chondrocytes, when released from lacunae, appeared to be disintegrating. However, in accord with previous evidence of their possible merger with chondroclasts (in light microscopic studies) there was also evidence for breakdown of cell walls between a chondroclast and a chondrocyte in intimate contact, with possibility of cytoplasmic continuity.     

Histological Development of the Fused Mandibular Symphysis in the Pig

The development of the mandibular symphysis in late fetal and postnatal pigs, Sus scrofa dom. (n = 17), was studied as a model for the early fusing symphysis of anthropoid primates, including humans. The suture-like ligaments occurring in species that retain a mobile symphysis are not present in the pig. Instead, cartilage is the predominant tissue in the mandibular symphysis prior to fusion. In late fetuses the rostrum of the fused Meckel's cartilages forms a minor posterior component of the symphysis whereas the major component is secondary cartilage, developing bilaterally and joined at the midline with mesenchyme. This remnant of Meckel's cartilage likely fuses with the flanking secondary cartilage. The overall composition of pig symphyseal histology in fetal and infant animals varies regionally and individually. Regions where the paired secondary cartilages abut in the midline resemble double growth plates. Chondrogenic growth in width of the symphysis is likely important in early stages, and central proliferation of mesenchyme is the probable source of new chondrocytes. Laterally, the chondrocytes hypertrophy near the bone fronts and are replaced by alveolar bone. Complete synostosis except for a small cartilage remnant had occurred in one 8-week-old postnatal specimen and all older specimens. Surprisingly, however, the initial phase of symphyseal fusion, observed in a 5-week-old postnatal specimen, involved intramembranous ossification of midline mesenchyme rather than endochondral ossification. Subsequently, fusion progresses rapidly at the anterior and labial aspects of the symphysis, leaving only a small postero-lingual cartilage pad that persists for at least several months. Anat Rec, 302:1372–1388, 2019. © 2018 Wiley Periodicals, Inc.     

Anatomy and Ontogeny of the Mandibular Symphysis in Alligator mississippiensis

Crocodylians evolved some of the most characteristic skulls of the animal kingdom with specializations for semiaquatic and ambush lifestyles, resulting in a feeding apparatus capable of tolerating high biomechanical loads and bite forces and a head with a derived sense of trigeminal-nerve-mediated touch. The mandibular symphysis accommodates these specializations being both at the end of a biomechanical lever and an antenna for sensation. Little is known about the anatomy of the crocodylian mandibular symphysis, hampering our understanding of form, function, and evolution of the joint in extant and extinct lineages. We explore mandibular symphysis anatomy of an ontogenetic series of Alligator mississippiensis using imaging, histology, and whole mount methods. Complex sutural ligaments emanating about a midline-fused Meckel's cartilage bridge the symphysis. These tissues organize during days 37–42 of in ovo development. However, interdigitations do not manifest until after hatching. These soft tissues leave a hub and spoke-like bony morphology of the symphyseal plate, which never fuses. Interdigitation morphology varies within the symphysis suggesting differential loading about the joint. Neurovascular canals extend throughout the mandibles to alveoli, integument, and bone adjacent to the symphysis. These features suggest the Alligator mandibular symphysis offers compliance in an otherwise rigid skull. We hypothesize a fused Meckel's cartilage offers stiffness in hatchling mandibles prior to the development of organized sutural ligaments and mineralized bone while offering a scaffold for somatic growth. The porosity of the dentaries due to neurovascular tissues likely allows transmission of sensory and proprioceptive information from the surroundings and the loaded symphysis. Anat Rec, 302:1696–1708, 2019. © 2019 American Association for Anatomy     

Autophagy Prior to Chondrocyte Cell Death During the Degeneration of Meckel's Cartilage

The central portion of Meckel's cartilage degenerates almost immediately after birth. Whether autophagy is involved in this process remains unclear. Thus, to explore the role of autophagy during this process, we have detected the expression of autophagy and apoptosis‐related markers in embryonic mice. In E15, Beclin1 and LC3 expressions were weak and negative in Meckel's cartilage, respectively. In E16, chondrocytes of the central portion became hypertrophic. Moderate immunoreactivities of Beclin1 and LC3 were observed in prehypertrophic and hypertrophic chondrocytes of the central portion. In E17, the degradation occurred in the central portion and expanded anteriorly and posteriorly. Beclin1 expression was observed in Meckel's cartilage with an increase in the hypertrophic chondrocytes of the central portion. The expression of LC3 was detected specifically in terminally differentiated hypertrophic chondrocytes. The mRNA expressions of LC3 and Beclin1 from E15 to E17 significantly increased. This result is in accord with the histologic findings. Terminal deoxynucleotidyltransferase‐mediated dUTP‐biotin nick‐end labeling assay and Caspase 3 expression demonstrated that apoptosis was detected in the lateral part of terminal hypertrophic chondrocytes along the degeneration area of Meckel's cartilage. In addition, Bcl2 expression increased significantly from E15 to E17. These results indicate that autophagy is involved in hypertrophic chondrocytes during the degradation of Meckel's cartilage and occurs prior to chondrocyte cell death during this process. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Stage-specific expression patterns of alkaline phosphatase during development of the first arch skeleton in inbred C57BL/6 mouse embryos

Timing and pattern of expression of alkaline phosphatase was examined during early differentiation of the 1st arch skeleton in inbred C57BL/6 mice. Embryos were recovered between 10 and 18 d of gestation and staged using a detailed staging table of craniofacial development prior to histochemical examination. Expression of alkaline phosphatase is initiated at stage 20.2 in the plasma membrane of mesenchymal cells in the distal region of the first arch. Expression is strongest in osteoid (unmineralised bone matrix) and presumptive periosteum at stage 21.32. Mineralisation begins at stage E23. Expression is present in the mineralised bone matrix. Secondary cartilages form in the condylar and angular processes by stage M24. The cartilaginous cells and surrounding cells in the processes are all alkaline phosphatase-positive and surrounded by the common periosteum, suggesting that progenitor cells of the processes, dentary ramus and secondary cartilages all originate from a common pool. Nonhypertrophied chondrocytes of Meckel's cartilage express alkaline phosphatase at stage M23. Expression in these chondrocytes is preceded by the expression in their adjacent perichondrium. This is true of chondrocytes in all other cranial cartilages examined. 3-D reconstruction of expression in Meckel's cartilage also revealed that the chondrocytes of Meckel's cartilage which express alkaline phosphatase and the matrix of which undergoes mineralisation are those surrounded by the alkaline phosphatase-positive dentary ramus. By stage 25, coincident with mineralisation in the distal section of Meckel's cartilage, most chondrocytes are strongly positive. The perichondria of malleus and incus cartilages express alkaline phosphatase at stage M24. Nonhypertrophied chondrocytes along these perichondria also express alkaline phosphatase. Superficial and deep cells in the dental laminae of incisor and 1st molar teeth become alkaline phosphatase-positive at the bud stage, stages 21.16 and 21.32, respectively. Dental papillae are negative until stage M24 when alkaline phosphatase expression begins in the dental papillae and follicles of the incisor teeth and the dental follicles of the 1st molar teeth. The dental papillae of the 1st molar teeth express alkaline phosphatase at stage 25. Expression in the dental papillae and follicles appears to coincide with cellular differentiation of follicle from papilla. The presumptive squamosal, ectotympanic and gonial membrane bones, lingual oral epithelial cells connected to the dental laminae of the incisor teeth, hair follicle papillae and sheath and surrounding dermis all express alkaline phosphatase in a stage-specific manner.     

Development of cartilage and bone tissues of the anterior part of the mandible in cichlid fish: A light and TEM study

The present paper presents ultrastructural details of chondrogenesis of Meckel's cartilage and of ossification of its associated peri- and parachondral bones in a teleost fish, the cichlid Hemichromis bimaculatus. We have distinguished four stages during chondrogenesis, each of which is characterized by specific cellular and matrix features: blastema, primordium, differentiated cartilage and cartilage surrounded by perichondral bone. The blastema is characterized by prechondroblasts and the lack of cartilage matrix; the primordium by chondroblasts and the onset of secretion of matrix of fibrillar and granular nature; differentiated cartilage is characterized by chondrocytes and larger amounts of typical hyaline cartilage matrix. Once perichondral bone is laid down, the chondrocytes show degenerative features but not true hypertrophy. Differentiation of the cartilage cells is attended with cytoplasmic changes indicative of an increasing secretory activity. There is a regional calcification of the cartilage matrix by fusion of calcospherites. Chondrogenesis of the symphyseal area is continuous with that of the rami but starts slightly later. Formation of perichondral bone at the cartilage surface is attended with the deposition of a transitional zone apparently containing a mixture of the two matrices. The role of the perichondral cells is discussed and it is proposed that they may contribute to the formation of the two matrices. The transitional zone may then result either from a diffusion process or from the simultaneous deposition of elements of the two matrices. Growth of the cartilage is argued to be largely the result of matrix secretion, except in the symphyseal area where appositional growth probably occurs until the region is completely covered by perichondral bone. This paper provides a basis for further studies on the developmental interactions between cartilage, bone and teeth during mandibular development in cichlids. © 1992 Wiley-Liss, Inc.     

A study of fine structural changes in the cartilage-to-bone transition within the developing chick vertebra

Forty-eight chick embryos were killed at 9–16 days of incubation age. Tissue was obtained from the fourth or fifth cervical vertebra, immersed in Karnovsky's fluid, post-fixed in osmium tetroxide, dehydrated in ethanol, stained “en bloc” with uranyl acetate in ethanol, and embedded in Epon 812. Vertebrae were oriented for cross-sectional microtomy in cephalic to caudal sequence. Thin sections were stained with uranyl and lead salt solutions saturated with tribasic calcium triphosphate to prevent decalcification. Chondrocytes within the cartilaginous vertebral body occur in various stages of degeneration without orderly arrangement. Both reversible and irreversible stages are found at the cartilaginous resorption front. Electron-lucent osteoid and mineralization appear in the intercellular matrix at about 12.5 days. Rapidly invading blood vessels form a highly variable resorption front and irregular marrow cavity. Capillaries with accompanying cells border on the front, but else-where open capillaries allow blood elements to be in direct contact with cartilage. Chondroclasts are associated with small areas of calcified cartilage. At about 14 days trabeculae are formed at the resorption front by osteoblasts which deposit bone osteoid on uncalcified cartilaginous matrix. The matrix is eroded away. A free trabecula of bone without a core of calcified cartilaginous matrix remains. Basic differences between developmental growth processes in the epiphyseal plate and vertebral body may stem from the large amount of uncalcified cartilaginous matrix at the latter's resorption front.     

Perspectives: A vital biomechanical model of the endochondral ossification mechanism

Background: Mechanical usage effects could explain many features of endochondral ossification and related processes. Mineralization of growth plate cartilage could reduce its mechanical strains enough to make its resorption begin and to guide it in space. By removing most of its mineralized vertical septae, resorption could overload the remainder enough to increase woven bone formation on them and construct the primary spongiosa. After it finishes mineralizing, the primary spongiosa could become stiff enough to begin partial disuse in strain terms, so BMU-based remodeling would begin replacing it with lamellar bone. This would construct the secondary spongiosa. In transferring loads from the growth plate to the cortex, the central metaphyseal spongiosa becomes deloaded. This disuse would make remodeling remove it in the diaphyseal marrow space. Methods: The slow growth of epiphyses and apophyses gives their spongiosas more time to adapt to their loads than the metaphyseal spongiosa beneath faster growing growth plates. Compared to metaphyseal trabeculae, this leads to fewer and thicker epiphyseal trabeculae that turn over more slowly and should persist for life because they carry loads for life. Results: Rapid turnover of metaphyseal cortex in very young subjects could let it strain enough to form woven bone. Increased thickness and slower turnover of this cortex in older subjects could reduce its strains enough to make lamellar bone form there instead. This would compose this cortex mostly of woven bone in the very young and of lamellar bone in adults. Conclusions: This model assigns particular importance to the stiffness and strains of tissues (as distinguished from their strength and stresses), to the relative rates of some processes, and to responses of the skeleton's biologic mechanisms to a tissue's typical largest mechanical strains (as distinguished from their stresses). © 1994 Wiley-Liss, Inc.     

Epithelial influences on skeletogenesis in the mandible of the embryonic chick

Intact mandibular processes and the enzymatically separated mesenchymal and epithelial components of the mandible from embryonic chicks of 2.5- to 5-day incubation (Hamburger and Hamilton, '51: stages 16-25) were grown individually, either in organ culture or as grafts to the chorioallantoic membranes of host embryos. The differentiation of cultured and grafted intact mandibular processes was histologically normal, but the time of histodifferentiation differed from that in vivo. The histodifferentiation of cultured and grafted mandibular mesenchyme grown isolated from its epithelium depended upon the age of the embryo from which the mesenchyme had been obtained. Intramembranous ossification producing membrane bones of the mandible occurred in mesenchyme isolated from 4.5- to 5-day embryos (HH 24–25), but did not occur in mesenchyme isolated from younger embryos. Cartilage (Meckel's) and subperichondrial bone in the articular process of Meckel's cartilage differentiated in mesenchyme isolated from embryos of all age groups tested (HH 16–25). Mandibular mesenchyme, therefore, requires the presence of epithelium until 4.5 days of incubation if the membrane bones of the mandible are to differentiate; if epithelial influences are required for Meckel's cartilage and subperichondrial bone formation, they are not required beyond 2.5 days of incubation. Mandibular epithelium isolated from its mesenchyme became layers of squamous cells in culture; but when grafted onto the chorioallantoic membrane, the epithelium became underlain by host fibroblasts and differentiated into a stratified squamous epithelium. Mandibular epithelium, therefore, is capable of differentiation in the presence of foreign fibroblasts derived from the chorioallantoic membrane.     

American association of anatomists nomination for membership forms

Previous studies of the turnover of alveolar bone collagenous proteins have devoted little attention to the variable patterns in this process caused by bone remodeling. The present study seeks to document changes resulting from physiologic tooth movements in the incorporation and removal of the ³H-proline label within the interdental septum of alveolar bone. One week following ³H-proline injection, three zones could be distinguished: (1) the appositional band, (2) new bone, and (3) old bone. Radioautography demonstrated that formation of new bone on the distal wall of the septum entrapped fibers of the periodontal ligament to create Sharpey's fibers. At the alveolar crest, new bone entrapped transseptal fibers to form transalveolar Sharpey's fibers. Grain counts were made within each area and over the total septum and were compared statistically. The data strongly suggested regional variations in protein remodeling. Counts from old and new bone were significantly different from the total septum or the appositional band (P < .001). Regression lines were drawn to represent incorporation and removal of the isotope; slopes were calculated and compared statistically. The rate of incorporation and removal was significantly greater in the appositional band and in the total septum in comparison to old bone (P < .001). The rates of incorporation and removal in the appositional band, old bone, and total septum were significantly different (P < .001). Half-life of the labeled protein of old bone was 16.78 weeks; in the appositional band, 7.66 weeks; and in the total septum, 7.64 weeks. These data suggest that regional variations in collagen remodeling must be considered in a study of interdental bone and that the total septal grain counts are not indicative of the remodeling in the component zones.     

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.     

Osteoarthritis-like disorder in rats with vascular deprivation-induced necrosis of the femoral head.

The reparative processes following vascular deprivation-induced necrosis of the femoral head were studied histologically in rats sacrificed 2, 7, 14, 21, 42 and 92 days postoperatively. The blood supply was severed by incision of the periosteum at the neck of the femoral head and transection of the ligamentum teres. Granulation tissue and a well-vascularized fibrous tissue originating from the joint capsule invaded the necrotic marrow spaces. With progressive resorption of the necrotic tissues and osteoneogenesis, both appositional and intramembranous, within the fibrotic intertrabecular spaces, the remodeling process led to a shift of the normal spongy architecture of the femoral head to a compacta-like one. In a few cases, osseous bridges bisected a necrotic physeal cartilage at the latest time intervals. The remodeling was associated with flattening of the femoral heads as well as with degenerative, regenerative and reparative alterations of the articular cartilage. In one of the two femoral heads obtained three months postoperatively, cystic spaces developed in the fibrous subchondral zone. Our findings are consistent with the view that ineffective attempts at restoring the prenecrotic state of the femoral head by replacing the necrotic with viable tissue triggers the collapse of the femoral head. Thickening and condensation of the subchondral bone, leading to increased stiffness of the subchondral zone, result in the osteoarthritis-like disorder. Mimicking the well-known phases of human osteonecrosis, the model readily allows for preclinical studies of therapeutic regimens.     

Meckel's cartilage in the human embryo and fetus

This work studied the development of the ventral part of Meckel's cartilage in a series of human embryos (classified in stages) and fetuses. These stages appeared particularly important: stage 16, appearance of Meckel's cartilage; stage 20, beginning of membranous ossification of mandible; and stage 23, end of the embryonic period (8th week). The primitive bony nodule which develops from the embryonic mesenchyme appears as a double bony layer forming a groove containing the neurovascular bundle, into which the dental lamina is also invaginated. It was concluded that during the fetal period, the cartilage participates in the formation of the body of the mandible in an area close to the mental foramen via endochondral ossification. The cartilage disappears in parallel with the development of ossification by the sixth month. © 1994 Wiley-Liss, Inc.