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PubMed1998

[Ossification of pulmonary tissue].

Two cases of pulmonary ossification found in postmortems were described. The first case, a 67-year-old stop-smoker with systemic hypertension died of a ruptured atherosclerotic aneurysm of the abdominal aorta. A well-defined subpleural mass (52 mm in max. dimension) was composed of monotonous mature trabecular osseous tissue with two focuses of cartilage up to 500 microns. There was no evidence of occluded blood supply and chronic passive congestion in the pulmonary parenchyma. A diagnosis of mesenchymoma (osteohamartoma) with the predominance of osseous tissue was made. The second case, a 72-year-old man non-smoker died of urosepsis. There were no pulmonary symptoms in patient's previous history. A well-defined ovoid mass (25 mm in diameter) was subpleurally located. Microscopically, it was formed of small nodules of mature lamellar bone together with branching bony deposits of trabecular character. Moreover, there were multiple smaller focuses scattered in the distant pulmonary tissue having appearance of nodular ossification. The evidence of chronic thromboembolic pulmonary disease together with ossification in microscopy permits the possibility that the nodular ossification may develop from pulmonary scarring or hemorrhagies as a late consequence of the thromboembolic pulmonary disease.

Aged↗
PubMed2000

Delayed membranous ossification of the cranium associated with familial translocation (2;3)(p15;q12).

The relationship of delayed membranous cranial ossification to cranium bifidum and parietal foramina syndromes is unclear. We report on a family with delayed cranial membranous ossification (OMIM 155980) that segregates with an apparently balanced reciprocal translocation between chromosomes 2 and 3. The propositus had apparently low-set ears, proptosis, and a soft skull at birth. A radiographic survey of the skeleton showed markedly decreased ossification of the cranial bones and no other skeletal abnormalities. The mother and maternal grandmother of the propositus have brachycephaly, hypertelorism, and a history of a soft skull at birth. Chromosome analysis of peripheral blood from the propositus showed 46,XY,t(2;3)(p15;q12). The propositus, mother, and grandmother carry the same reciprocal translocation, whereas the mother's two phenotypically normal sibs have a normal karyotype. We used an STS-linked BAC resource to define the translocation breakpoint by identifying flanking BAC clones from both chromosomes 2, 1006D24 (D2S2279) and 1060A5 (D2S2231), and chromosome 3, 3D17 (WI8558) and 3D18 [CITB Human BAC Library, J.R.K.]. This represents the second report of a family with delayed membranous ossification of the cranium and the first report of the phenotype segregating with a chromosome rearrangement.

Adult↗
PubMed1995

Chondrocyte apoptosis in endochondral ossification of chick sterna.

In the process of endochondral ossification, chondrocytes progress through a series of maturational changes, including division and hypertrophy, that culminate in chondrocyte loss and cartilage resorption. From an investigation of morphology, DNA fragmentation and collagen synthesis in the developing chick sterna we have characterized chondrocytes death in this process. Light microscopy of resorbing sterna demonstrated chondrocyte condensation at the interface with the invading vasculature and electron microscopy demonstrated a range of chondrocyte morphologies, including retraction from the pericellular matrix, cytoplasmic and nuclear condensation, and vesiculation suggestive of sequential changes characteristic of apoptosis. Isolation and end-labeling of DNA from chick primary ossification centers demonstrated fragmentation to nucleosome sized units, only in primary ossification centers exhibiting active resorption, and in situ detection of DNA fragmentation showed a restriction to chondrocytes at the interface with invading blood. We conclude that terminal differentiation of chondrocytes results in death by an apoptotic process prior to resorption of the tissue and invasion by blood vessels. The extent of DNA fragmentation correlated closely with the proportion of cells displaying a condensed phenotype in contralateral primary ossification centers and peaked at an early stage of resorption, suggesting that chondrocyte apoptosis may be an initiating event in tissue resorption and vascular invasion. Comparison of DNA fragmentation with expression of the hypertrophic chondrocyte phenotype, as indicated by type X collagen synthesis, suggested that DNA fragmentation was a late event in the process of chondrocyte hypertrophy and probably corresponded with chondrocyte condensation

Animals↗
PubMed2004

Ossification and midline shape changes of the human fetal cranial base.

An appreciation of ontogenetic changes to the cranial base is important for understanding the evolution of modern human skull form. Using geometric morphometric techniques, this study explores midline shape variations of the basicranium and midface during human prenatal ontogeny. In particular, the analysis sets out to explore shape variations associated with endochondral ossification and to reassess shape variations previously observed on the basis of angular measures.Fifty-four formalin-preserved human fetuses were imaged using high-resolution MRI. Coordinates for 10 landmarks defining the midline basicranium and midface were acquired and areas of ossification in the midline basioccipital, basisphenoid, and presphenoid cartilages were measured as percentages of overall cranial base area. The results show shape variations with increasing fetal size that are consistent with cranial base retroflexion, anterior facial projection and dorsal facial rotation. These growth variations are centered on the midsphenoid area and are associated with disproportionate variations of sphenoid height and length. Small but significant correlations were observed between ossification of the presphenoid cartilage and components of shape that described, among other variations, sphenoid shortening. While ossification cannot be directly linked with the shape variations observed, it seems likely that bone formation plays a role in modulating the influence of other factors on the fetal cranial base.

Biological Evolution↗
PubMed1978

Ossification in the hand and foot of the macaque (Macaca nemistrina). I. General features.

The appearance of the secondary centers of ossification was investigated in hand and foot radiographs of 112 fetal and neonatal Macaca nemestrina and a maturational index calculated using a scoring system that differentiated between the initial and later stages of ossification. Cumulative incremental curves of skeletal maturation, constructed by plotting the maturational indices against gestational age, demonstrated three distinct periods of ossification: the First Acceleration when primary centers appear, the Plateau, and the Second Acceleration when the secondary centers ossify. Similar curves are constructed for human prenatal and postnatal ossification. The results are also compared with those reported for M. mulatta, and the bases of the observed differences are discussed. Compared with other primates, the fetal and neonatal macaque shows a developmental precocity which may be an ontogenetic adaptation to the socioecological setting of terrestrial life.

Animals↗
PubMed1995

Basement membrane composition of cartilage canals during development and ossification of the epiphysis.

BACKGROUND: Cartilage canals are perichondral invaginations of blood vessels and connective tissue that are found within the epiphyses of most mammalian long bones. Functionally, they provide a means of transport of nutrients to the hyaline cartilage, a mechanism for removal of metabolic wastes, and a conduit for stem cells that are capable of initiating and sustaining ossification of the chondroepiphysis. Morphological and biomolecular changes of the chondroepiphyses appear to potentiate ossification within the chondroepiphyses of developing bones. METHODS: As both cell migration and vascular invasion are anchorage dependent processes, antibodies to laminin and Type IV collagen were used to assess compositional changes in the basement membrane of cartilage canals accompanying epiphyseal ossification. RESULTS: Differences in chronological appearance, as well as, in distribution between the two components were noted in the chondroepiphysis. Laminin was distributed throughout the connective tissue of cartilage canal at all stages of development, and not limited to an association with the vascular lumen. Type IV collagen was not present during the initial perichondral invagination. Although staining for Type IV collagen was later acquired, its distribution was restricted to a discontinuous rimming of the periphery of the canal, and a diffuse presence within the intra-canalicular mesenchyme. CONCLUSIONS: Concurrent with chondrocyte hypertrophy and mineralization of the hyaline matrix, rapid changes in both the morphology of the vessel and distribution of the antibodies were detected. In addition to the presence of laminin at the interface of the endothelium and the hyaline matrix, a wide distribution within the connective tissue components of the newly ossifying matrix of epiphyseal bone could be detected. Type IV collagen remained closely associated with the lumens of the intra-canalicular vessels throughout the transition. Following ossification of the secondary center, staining for Type IV collagen could then be detected in the bone-forming regions of transforming matrix as well, clearly delineating the individual vessels within the newly formed marrow spaces. This suggests that bone formation is intimately related to vessel staining for collagen type IV, and that acquired vessel competence is a facet of endochondral bone formation that results from provisional matrix changes. Furthermore, the data suggests that during bone formation under tension, basement membrane deposition can be demonstrated without an intermediary hyaline matrix hypertrophic chondrocyte phase. This data was interpreted to suggest that chondrocyte hypertrophy at the growth plate may be a reaction to vascular invasion, that in turn, stimulates adjacent chondrocyte proliferation.

Animals↗
PubMed2005

Assessing age-related ossification of the petro-occipital fissure: laying the foundation for understanding the clinicopathologies of the cranial base.

The petro-occipital fissure (POF) lies within a critical interface of cranial growth and development in the posterior cranial fossa. The relationships between skeletal and soft tissues make this region especially important for examining biomechanical and basic biologic forces that may mold the cranial base and contribute to significant clinicopathologies associated with the structures located near the POF. Therefore, this study investigates the POF in adults in both preserved human cadavers and dried crania in order to determine if developmental changes can be observed and, if so, their value in age assessment as a model system for describing normal morphogenesis of the POF. This study demonstrates that tissue within the POF undergoes characteristic changes in ossification with age, the onset of which is considerably later than that of other synchondroses of the cranial base. Statistically, there is a moderate to strong correlation between age and stage of ossification within the POF. Further, male crania were observed to reach greater degrees of ossification at a younger age than female crania and that individual asymmetry in ossification of the tissue within the POF was not uncommon. An understanding of the basic temporal biological processes of the POF may yield insight into the development of clinicopathologies in this region of the cranial base.

Adult↗
PubMed2005

Expression of Semaphorin-3A and its receptors in endochondral ossification: potential role in skeletal development and innervation.

Bone tissue is densely innervated, and there is increasing evidence for a neural control of bone metabolism. Semaphorin-3A is a very important regulator of neuronal targeting in the peripheral nervous system as well as in angiogenesis, and knockout of the Semaphorin-3A gene induces abnormal bone and cartilage development. We analyzed the spatial and temporal expression patterns of Semaphorin-3A signaling molecules during endochondral ossification, in parallel with the establishment of innervation. We show that osteoblasts and chondrocytes differentiated in vitro express most members of the Semaphorin-3A signaling system (Semaphorin-3A, Neuropilin-1, and Plexins-A1 and -A2). In vitro, osteoclasts express most receptor chains but not the ligand. In situ, these molecules are all expressed in the periosteum and by resting, prehypertrophic and hypertrophic chondrocytes in ossification centers before the onset of neurovascular invasion. They are detected later in osteoblasts and also osteoclasts, with differences in intensity and regional distribution. Semaphorin-3A and Neuropilin-1 are also expressed in the bone marrow. Plexin-A3 is not expressed by bone cell lineages in vitro. It is detected early in the periosteum and hypertrophic chondrocytes. After the onset of ossification, this chain is restricted to a network of cell processes in close vicinity to the cells lining the trabeculae, similar to the pattern observed for neural markers at the same stages. After birth, while the density of innervation decreases, Plexin-A3 is strongly expressed by blood vessels on the ossification front. In conclusion, Semaphorin-3A signaling is present in bone and seems to precede or coincide at the temporal but also spatial level with the invasion of bone by blood vessels and nerve fibers. Expression patterns suggest Plexin-A3/Neuropilin-1 as a candidate receptor in target cells for the regulation of bone innervation by Semaphorin-3A.

Animals↗
PubMed2002

Comparative patterns of postcranial ontogeny in therian mammals: an analysis of relative timing of ossification events.

Data on the relative sequence of ossification of postcranial elements for eight therian mammals (Myotis lucifugus, Homo sapiens, Rattus norvegicus, Mus musculus, Mesocricetus auratus, Cavia porcellus, Didelphis albiventris, and Sminthopsis macroura) and three outgroups (Chelydra serpentina, Alligator mississippiensis, and Lacerta vivipara) were taken from the literature. For each species, a matrix was constructed in which the relative timing of the onset of ossification in 24 elements was summarized. This resulted in 276 event pairs (characters) for each species. Thirty-three (33.3)% of the characters examined are uniform across all taxa, 16.3% are variable but uninformative in the phylogeny, and 50.4% potentially deliver diagnostic features for clades of two or more taxa. In all species examined, the clavicle is the first bone to appear. Placentalia is not unequivocally diagnosed by the state of any event pair, while Marsupialia has the largest amount of autapomorphies with 18. The acceleration in the timing of ossification of the scapula in relation to the hindlimb in marsupials is most probably causally correlated to movements after birth and during early phases of pre-weaning life. Marsupials are almost unique among amniotes in that the earliest onset of ossification of at least one element among carpals and among tarsals is simultaneous. Three parsimony analyses, each one with a different reptilian taxon as outgroup, were performed using event pairs as characters. In all cases, results were incongruent with the phylogeny of the studied taxa.

Age Factors↗
PubMed2003

Patterns of ossification in the manus of the harbor porpoise (Phocoena phocoena): hyperphalangy and delta-shaped bones.

With the transition from terrestrial to aquatic habitats, cetacean forelimbs have undergone significant modifications in bone morphology and soft tissue distribution. Some, but not all, of these modifications are also demonstrated in other lineages of extant and extinct secondarily aquatic tetrapods. This study examines the ontogenetic pattern of ossification of the manus of the harbor porpoise (Phocoena phocoena), using plain film radiography. Two modifications examined are hyperphalangy (number of phalanges per digit increased beyond the typical mammalian number) and the morphology of delta-shaped bones. Hyperphalangy in Phocoena phocoena is apparent in digits 2 and 3. Phalangeal counts in all digits are variable (sometimes between the right and left flippers of the same individual) and are not necessarily correlated with age. Phalangeal ossification and epiphyseal fusion proceeds along the proximo-distal axis within each digit. In addition, digits 2 and 3 are at a more advanced stage of ossification than more abaxial digits. Delta-shaped bones appear to be a normal stage in the ossification of phalanges in all digits except the third, and may persist in the adult in certain digits. In humans, this morphology is a developmental anomaly usually associated with other malformations, such as polydactyly or syndactyly. Delta-shaped bones in the cetacean manus display a consistent orientation and the process by which they are formed may be similar to that in extinct marine reptiles.

Age Factors↗
PubMed1975

Prenatal ossification in rabbits as indicative of fetal maturity.

During the prenatal period of development of the rabbit skeleton (days 21-30) the successive phases of fetal maturity can be distinguished by reference to the progress of ossification, particularly in the distal limbs and sternum. In the present study absent or incomplete ossification of sternebra 5 occurred in 8% of term fetuses. The incidence of anomalies of prenatal ossification of the axial skeleton was 1.9%. The relevance of delayed and disturbed ossification with regard to teratological tests is discussed.

Animals↗
PubMed1979

The extent of fetal ossification as an index of delayed development in teratogenic studies on the rat.

In teratogenic studies toxic effects may manifest themselves in retarded fetal development, such as a reduction in fetal weight. In searching for an additional index, the number of centers of ossification in seven skeletal districts (sternum, metacarpus, metatarsus, cervical and caudal vertebrae, anterior and posterior proximal phalanges) of rat fetuses delivered on days 19, 20 and 21 of gestation were counted and compared. Results showed uneven ossification in day-19 and -20 fetuses, but sufficiently advanced, homogeneous and uniform ossification in day-21 fetuses to provide a reliable quantitative index for evaluating retarded fetal development. It is therefore proposed that the stage of skeletal ossification in day-21 fetuses be used in teratogenic studies in the rat to evaluate retarded fetal development.

Animals↗
PubMed1989

Prenatal ossification as an indicator of exposure to toxic agents.

Following exposure to bromodeoxyuridine (BUDR), acetazolamide (ACZM), trypan blue (TRBL), cortisone (CORT), or diphenylhydantoin (DPH), alizarin-stained, cleared fetuses were examined at 18 days postcoitus for unossified cervical vertebral centra; number of ossified caudal vertebrae; number of ribs; and ossification of sternebrae, metatarsals, metacarpals, and phalangeal rows. At all teratogenic doses, in no vehicle-treated groups, and rarely in lower-dose groups, there were significant increases in frequency of unossified cervical centra, the first vertebra (C1) being most often affected, and C7 least often affected. In the high-dose CORT group, there was a significant correlation between unossified C1 and cleft palate. No association between abnormality and reduced ossification of cervical vertebrae was seen in other series examined, nor was there any correlation between litter size and abnormality. With minor complications, the number of ossified caudal vertebrae was significantly reduced after exposure at teratogenic dose levels to all compounds except DPH. Although caudal and cervical ossification were correlated with each other in those series examined, neither was correlated with abnormality. Frequency of 14 ribs was increased in BUDR, ACZM, and TRBL but not CORT or DPH. Other parameters were essentially unaffected. Significantly increased frequency of abnormality, when contrasted with untreated or vehicle-treated groups, was seen at high-dose levels in all but DPH treatments, and mortality was increased in ACZM D9-11, TRBL, and CORT. These studies show that reduced ossification of cervical centra is an excellent indicator of prenatal exposure to noxious substances, and caudal vertebrae appear to be useful as well. Increased frequency of 14 ribs occurred for all strong teratogens utilized if they were administered on day 7 or day 8 postcoitus.

Acetazolamide↗
PubMed1990

A theoretical model of endochondral ossification and bone architectural construction in long bone ontogeny.

The role of mechanical stresses in the formation of endochondral ossification patterns and the construction of basic bone architecture in human long bones is investigated using a three-dimensional generalized model of long bone development. The distribution of mechanical stress which is created in developing bones as a result of intermittent mechanical loading is calculated using a computer model that mathematically represents the bone's geometry, material properties and loading conditions. The process of endochondral ossification is simulated by iteratively converting cartilaginous regions of the computer model to bone, based on the calculated intermittent hydrostatic and shear stress distributions. Once local regions of mineralized bone have formed, these regions are remodeled according to an algorithm which relates bone density to a mechanical stress stimulus. The results simulated the correct sequence of the appearance of morphological structures which are common to long bones in the human appendicular skeleton. These developmental structures include the site of the first endochondral bone and the secondary ossification center and the tubular nature of long bones. Our results suggest that mechanical loading histories may influence bone morphogenesis beginning from the early stages of endochondral ossification and continuing throughout life. The stress-based algorithms may be part of the 'rules of construction' or 'developmental constraints' which guide limb ontogeny.

Algorithms↗
PubMed1976

The onset of ossification in the human calcaneus.

A (silver) radiographic and microscopic study of the onset of ossification in the calcaneus of 177 human fetuses between 49 and 150 mm C.-R. length has revealed the presence of two independent and developmentally different ossific sites. A lateral locus, intramembranous (parachondral) in origin and precocious in appearance, was observed in slightly over 16% of the fetuses examined between 93 mm (the first appearance of this bone) and 150 mm C.-R. It occupied the vascular connective tissue within the anterior portion of a distinct groove on the inferolateral wall of the cartilaginous calcaneus between the retrotrochlear eminence anterosuperiorly, and the lateral process of the tuber posteroinferiorly. A centrally situated, primary ossific centre, endochondral in origin, was detected in only 11% of the fetuses between 118 mm (the initial appearance of this centre) and 150 mm C.-R. It was situated in the centre of the anterior third of the cartilaginous calcaneus in relation to the sustenaculum tali medially and to a distinct cartilaginous prominence on its lateral surface. Only four fetuses possessed both ossific sites (lateral and central): at 122, 143, 145, and 150 mm C.-R., and in only one of these was continuity established between them. One fetus (122 mm) possessed two independent endochondral centres (superior and inferior).

Calcaneus↗
PubMed1980

Ossification of the skull of the growing hamster. Autoradiographic observations.

Desmal ossification of the roof of the skull and of the alveolus of the incisor teeth of the mandible of growing hamsters and secondary ossification of the mandible were followed by autoradiography. Matrix production patterns as known from chondral ossification can be confirmed for desmal ossification as well. The secondary cartilage of the mandible shows an extremely low glycine turnover. These cells and the surrounding intercellular substance show different incorporation patterns as known for the epiphyseal cartilage of long bones. Secondary cartilage does not have growth functions for the mandible.

Animals↗
PubMed1993

Epiphysial ossification centres in iliosacral joints: anatomy and computed tomography.

Bilateral apparently bony structures of different forms and sizes located in the inferior and superior ventral parts of the sacroiliac joints were observed on axial CT images of the pelvic region of juvenile patients. No other pathological changes were noted in the sacroiliac joints of these individuals. In one patient the bony structures could also be seen on a conventional plain radiograph. We also examined 3 juvenile autopsy specimens of this joint using radiology, CT, macroscopical evaluation and histology. In two of them, structures could be detected on the CT scans which were similar to those observed in the young patients. Macroscopic investigations revealed the structures to be secondary ossification centres located in the articular cartilage of the lateral part of the os sacrum at the levels of the first and third sacral segments. According to older anatomical literature, these epiphysial ossification centres contribute to the auricular surface of the lateral part of the os sacrum and the free lateral surface of the inferior sacral parts. They can be observed between the ages of 12 and 25 years and begin to synostose with the lateral part around the age of 18 years. In macerated juvenile specimens of the bony pelvis, free ossicles were not detectable in the region of the sacroiliac joints. Histological peculiarities of the ossification process observed are discussed. These physiologically occurring ossification centres are to be differentiated from pathological alterations appearing as bony or bone-like structures on CT scans.

Adolescent↗
PubMed1990

Accessory ossification centres at the thoracolumbar junction.

A survey of 810 thoracolumbar junction CT scans demonstrated several forms of accessory ossification centres and vestigial ribs associated with the posterior element processes. Four examples of short T12 ribs and 15 L1 ribs were identified, in addition to 8 accessory ossification centres at L1, and 3 at T12. Radiographic features of accessory ossification centres were compared with histologic characteristics from cadaver studies. Accessory ossification centres have occasional clinical significance when they may be confused with fractures at the thoracolumbar junction. Differential diagnosis relies on adequate visualization of their cortical margins to distinguish them from recent fractures of the processes.

Adult↗