SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
The calcified tissues involved in the early morphogenesis of the so-called intramembranous bones of the facial skeleton were studied by microradiographic and histological techniques in 22 chick embryos at the 9th, 12th and 14th days of incubation. On the 9th day, the bones of the upper face and palatal vault are made up of thin sheets of chondroid tissue, deposited in their respective mesenchymal condensations. Woven and lamellar bone formation subsequently takes place in each of them from the 12th day of incubation, mainly on the external side of their chondroid primordia. The same phenomena occur in the lower facial and mandibular bones. These facts indicate that the primitive facial desmocranium of the chick embryo, which is classically considered to be formed by intramembranous ossification, first consists of chondroid tissue. As in the cranial vault, this tissue thus represents the initial modality of the skeletogenic differentiation within the avian facial mesenchyme.
Osteological characteristics are often used to identify animal species in a cheap and rapid manner. In this context it is believed that the corpus fibulae of the goat is represented by a tight cord of connective tissue--the so-called ligamentum fibulare. The results of the present morphometric study indicate, however, that in nearly 60% of the 143 examined animals, the corpus fibulae is a pin-shaped flattened piece of bone which may additionally be accompanied by a pyramid-shaped bone lying closely to the caput fibulae. The length of the corpus fibulae increases with age and varies greatly between individuals but its centre is located close to the border between the proximal and the intermediate third of the tibia. The cartilaginous fetal anlage is either transformed to bone or catabolised during fetal live. Desmal ossification should play an important role in the growth of the corpus fibulae since no cartilage could be detected in kids and adult goats.
UNLABELLED: We examined the role of caveolae and caveolin-1 in the mechanism of 1alpha,25(OH)(2)D(3) action in growth plate chondrocytes. We found that caveolae are required for rapid 1alpha,25(OH)(2)D(3)-dependent PKC signaling, and caveolin-1 must be present based on studies using chondrocytes from Cav-1(-/-) mice. INTRODUCTION: 1,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] regulates endochondral ossification in part through membrane-associated mechanisms, including protein kinase C (PKC) signaling activated by a membrane-associated 1alpha,25(OH)(2)D(3)-binding protein, ERp60. We tested the hypothesis that caveolae are required for 1alpha,25(OH)(2)D(3) action and play an important role in regulating chondrocyte biology and growth plate physiology. MATERIALS AND METHODS: Rat costochondral chondrocytes were examined for caveolae by transmission electron microscopy of cultured cells and of cells in situ. Western blots and confocal microscopy were used to detect caveolae proteins including caveolin-1 (Cav-1) and 1alpha,25(OH)(2)D(3) receptors. Caveolae cholesterol was depleted with beta-cyclodextrin (CD) and effects of 1alpha,25(OH)(2)D(3) on PKC, DNA synthesis, alkaline phosphatase, and proteoglycan production determined. Chondrocytes from Cav-1(-/-) and C57BL/6 wildtype mice were also treated with 1alpha,25(OH)(2)D(3). Epiphyses and costochondral junctions of 8-week-old male Cav-1(-/-) and wildtype mice (N = 8) were compared by histomorphometry and microCT. Data were analyzed by ANOVA and Bonferroni for posthoc comparisons. RESULTS: Growth zone chondrocytes had caveolae and Cav-1, -2, and -3. Resting zone chondrocytes, which do not exhibit a rapid 1alpha,25(OH)(2)D(3)-dependent increase in PKC activity, also had these caveolins, but caveolae were larger and fewer in number. ERp60 but not VDR co-localized with Cav-1 in plasma membranes and in lipid rafts. CD-treatment blocked 1alpha,25(OH)(2)D(3) effects on all parameters tested. The Cav-1(-/-) cells did not respond to 1alpha,25(OH)(2)D(3), although 1alpha,25(OH)(2)D(3) increased PKC, alkaline phosphatase, and [(35)S]-sulfate incorporation in wildtype C57BL/6 cells. Histology and microCT showed that Cav-1(-/-) growth plates were longer and had more hypertrophic cells in each column. Growth plate changes were reflected in the metaphysis. CONCLUSIONS: The membrane-mediated effects of 1alpha,25(OH)(2)D(3) require caveolae and Cav-1, and Cav-1 deficiency results in altered growth plate physiology.
In order to investigate further the effects of paralysis on skeletal development in the chick embryo, paralysis was induced at 6 days of incubation by dropping 0.2% solution of decamethonium bromide onto the chorioallantoic membrane and maintaining paralysis through to 20 days of incubation. General effects of paralysis included lower body weight, marked subcutaneous oedema, twisting of the neck to the right with marked rigidity, and protrusion of the lower beak beyond the upper. Skeletal abnormalities included cartilaginous and later bony fusion between cervical vertebrae and distortion of scapula and pubis. Long bones were normal in their general form but showed marked reductions in full length and in length of the calcified diaphysis. The patella occasionally underwent chondrification, unlike the tibial cartilage at the tarsus. Reduction in length of the bones of both jaws occurred but was substantially greater in the upper, resulting in the protrusion of the lower. Ossification times of most skeletal elements were little affected by paralysis but some centres appearing nearer the end of incubation showed slight delay in their times of appearance.
Members of the TGFbeta/BMP gene family regulate cartilage and bone development. These genes are re-expressed in bone repair and are thought to mediate chondro- and osteoprogenitor cell differentiation. These observations have led to a therapeutic strategy of introducing these growth factors into experimental cartilage and bone defects. Therapeutic efficacy, however, has been limited by diffusion or inactivation of these growth factors from the desired site and by the inability to deliver sustained concentrations of growth factors. This study demonstrates an increase in basal TGFbeta mRNA and protein levels in association with chondrogenic differentiation in endochondral ossification. mRNA is increased by 158%; protein by 23%, and cells immunopositive for TGFbeta by 343% at maximal TGFbeta expression. Importantly, the pattern of TGFbeta expression is preserved throughout the developmental sequence. Our data suggest that the exposure to a specific electromagnetic field (EMF) enhances, but does not disorganize, chondrogenesis and endochondral calcification as well as the normal physiologic expression of TGFbeta. The ability to increase TGFbeta at a moderately low dose for sustained periods of time without disorganizing its physiology suggests the ability to establish temporal concentration gradients of growth factors for the purpose of stimulating skeletal repair.
In the hindbrain region of the developing CNS, anteroposterior patterning involves a transient segmentation process which leads to the formation of morphological bulges called rhombomeres. The rhombomeres constitute cell lineage restriction units and participate in the establishment of a metameric pattern which is responsible for the segmental organisation of motor and reticular neurons. Like Drosophila compartments, rhombomeres also constitute domains of specific gene expression. Genes expressed in a rhombomere-specific manner so far identified encode various types of putative regulatory molecules, including transcription factors, like Hox proteins, the zinc finger protein Krox-20 and the basic domain leucine-zipper protein kreisler, and receptor type molecules, like Sek-1, a member of the EPH family of tyrosine kinase receptors. Such genes are thought to play a role either in the definition of segmental territories or in the specification of the identity of the rhombomeres. Initial analysis of the function of some of these genes have indeed supported this hypothesis. This is the case for the Krox-20 gene. It is expressed within the developing hindbrain in two transverse domains which prefigure and then coincide with r3 and r5. We have inactivated Krox-20 by homologous recombination in ES cells and demonstrated that the mutation leads to the deletion of r3 and r5. The mutation introduced into the Krox-20 gene involved the in-frame insertion of the lacZ coding sequence. This allowed us to follow the late expression pattern of the gene and to identify two additional phenotypes, affecting myelination of the peripheral nervous system and endochondral ossification. The lacZ reporter also permitted a detailed analysis of the expression of Krox-20 in peripheral glial cells, revealing important steps in the control of their development. Recently we have performed a detailed analysis of specific neuronal populations affected by the mutation which shed new light on the role of Krox-20 in the segmentation and on the physiological consequences of its inactivation. We have also identified several new members of the Sek-1 family of receptor tyrosine kinases, which are also expressed in a rhombomere-specific manner. Finally, we have provided evidence that Krox-20 is as a key regulator of r3/r5-specific transcription, controlling the expression of at least five other regulator genes in these rhombomeres. In three cases, Hoxb-2, Hoxa-2 and Sek-1, we could demonstrate that Krox-20 was directly involved in the transcriptional activation of these genes.
Skeletal malformations at metamorphosis in Rana perezi tadpoles reared in culture have been studied. Tadpoles were fed ten artificially compounded and fresh diets and kept at two different temperatures. Animals were maintained in fiberglass tanks. Bone damages are related to the nourishment with compound diets. Tadpoles fed such diets showed variable percentages of scoliosis, kyphosis, luxations, and subluxations in the hind limbs, aplasia in phalanges, and wide failures of ossification. The data suggest the origin of the lesions is a deficiency in some compounded diets that could alter collagen metabolism during skeletal adjustments at metamorphosis.
Disruption of the murine Mop3 (also known as Bmal1 or Arntl) locus results in a loss of behavioral and molecular circadian rhythms. Although Mop3 null mice do not display anomalies in early development, they do display reduced activity as they age. In an effort to explain this decreased activity, we characterized the physiological and anatomical changes that occurred with age. We observed that Mop3 null mice display an increased mortality after 26 weeks of age and a phenotype best described as a progressive noninflammatory arthropathy. Although little pathology is observed prior to 11 weeks of age, by 35 weeks of age essentially all Mop3 null animals develop joint ankylosis due to flowing ossification of ligaments and tendons and almost complete immobilization of weight-bearing and nonweight-bearing joints. This pathology appears to explain the decreased activity of Mop3 null mice and suggests that MOP3 is an inhibitor of ligament and tendon ossification.
Bone lengthening using the process of corticotomy and gradual distraction of callus is applicable to the membranous bone of the canine mandible. In this study the precursors to bone formation, in the area between the distracted bone edges, are analyzed in an attempt to determine the mechanism of bone formation. Ten mongrel dogs 5 months of age were studied. A unilateral, periosteal-preserving angular corticotomy was performed, and an external bone-lengthening device was fixed to the mandible. After 10 days of external fixation, the mandible was lengthened 1 ml per day for 20 days and then held in external fixation for 8 weeks. The dogs were killed for histological and microradiographic study at 10 and 20 days of distraction, and at 14, 28, and 56 days after the completion of distraction. It was observed that the gap between the distracted bone edges is first occupied by fibrous tissue. As distraction proceeds, the fibrous tissue becomes longitudinally oriented in the direction of distraction. Early bone formation advances along the fibrous tissue, starting from the cut bone ends. Eventually the area is converted to mature cortical bone. Bone is formed predominantly by intramembranous ossification. This mechanism is similar to that of bone formation during long bone lengthening.
We report the case of a patient with no otorhinolaryngologic symptoms who had an unusual radiological finding in the petrous bone secondary to congenital rickets. The impaired ossification of the rickets did not affect the compact bone of the otic capsule, making the bony labyrinth perfectly visible inside the temporal bone of osteoid substance.
Every form of osteoporosis--except the physiological involution osteoporosis--requires treatment. Osteoporosis is no disease by itself but a result or a concomitant phenomenon of various diseases. Therefore the primary disease has to be treated also. Only for the so-called idiopathic osteoporosis hitherto no cause is known. Today sodium fluoride is the only substance with an influence upon the bone which may induce re-ossification and re-stabilization. In the described series of investigations this compound, with which treatment by gradual dosage is possible, has proved its effectiveness. Osteoporosis is more than bone porosity, therefore additionally afflicted organic or functional system like the muscular apparatus, bone marrow, or the intraosseous blood supply, must be treated too. Psychological guidance of the patient is necessary as he must be motivated for activity.
The elucidation of patterns of cranial skeletal maturation and growth in fossil hominids is possible not only through dental studies but also by mapping different aspects of ossification in both extant African apes and humans. However, knowledge of normal skeletal development in large samples of extant great apes is flimsy. To remedy this situation, this paper offers an extensive survey and thorough discussion of the ossification of the posterior border of the sphenoid greater wing. Indeed, this area provides much information about basicranial skeletal maturation. We investigate three variants: the absence of the foramen spinosum and the position of both the foramen spinosum and the foramen ovale in relation to the sphenosquamosal suture. Providing original data about humans and 1,425 extant great ape skulls and using a sample of 64 fossil hominids, this study aimed to test whether different ossification patterns occurred during the course of human evolution. The incidence of three derived morphologies located on the posterior border of the sphenoid greater wing increases during human evolution at different geological periods. The evolutionary polarity of these three derived morphologies is assessed by outgroup comparison and ontogenetic methods. During human evolution, there is a clear trend for the foramen spinosum to be present and wholly located on the posterior area of the sphenoid greater wing. Moreover, in all the great ape species and in Australopithecus afarensis, the sphenosquamosal suture may split the foramen ovale. Inversely, the foramen ovale always lies wholly within the sphenoid greater wing in Australopithecus africanus, robust australopithecines, early Homo, H. erectus (and/or H. ergaster), and Homo sapiens. From ontogenetic studies in humans, we conclude that, during human evolution, the ossification of the posterior area of the sphenoid greater wing progressively surrounded the middle meningeal artery (passing through the foramen spinosum) and the small meningeal artery (passing through the foramen ovale).
One hundred and twenty adult and 80 human fetal skulls were examined to find the relationship (if any) between the presence of wormian bones in the lambdoidal suture and artificial deformation of the skull. Wormian bones occur in deformed and undeformed skulls with no significant differences. Wormian bones detected in fetal skulls preclude cultural deformation as an important factor in the formation of these bones. It is hypothesized that a genetic predisposition (genes allowing formation of secondary ossification centers) is present and that wormian bones are under direct genetic control regardless of the presence or absence of detectable cultural deformation.
In 157 spontaneously aborted human embryos and fetuses the incidence and evolution of coronal cleft formation was investigated radiologically and histologically. Complete clefts were formed in nine cases and incomplete clefts in 16 cases. There was a predominance of males. It is concluded that coronal clefts are variations of normal enchondral ossification and that the notochord plays no role in its pathogenesis. Coronal clefts seen on radiographs of newborn should not be interpreted as a malformation. Thus no preventive or treatment regimen is indicated.
Early molecular markers for flatfish metamorphosis and eye migration must be linked to the ethmoid region, the earliest part of the flatfish cranium to change, as well as chondral and dermal ossification processes. Serial sections, morphological landmarks, and stereology were used to determine where and when the remodeling of tissues and asymmetry occurs in the head region of metamorphosing Atlantic halibut, Hippoglossus hippoglossus. Not all parts of the head remodel or migrate, and those that do may be asynchronous. Normal metamorphosis limits the torsion of the Atlantic halibut head to the anterior part of the neurocranium and excludes the tip of the snout and the general jaw area. The first cranial structure displaying eye migration-related asymmetric development is the paraethmoid part of the ethmoid cartilage. In early eye migration the medial frontal process moves apace with the eyes, whereas near completion the migrating eye moves significantly closer to the frontal process. Structures of the jaw remain mostly symmetrical, with the exception of the adductor mandibulae muscle and the bone maxillare, which are larger on the abocular than on the ocular side, the muscle occupying the space vacated by the migration of the eye. Thus, normal eye migration involves a series of temperospatially linked events. In juveniles lacking eye migration (arrested metamorphosis), the dermal bone, the prefrontal, does not develop. The two abnormal paraethmoids develop symmetrically as two plate-like structures curving anteriorly, whereas normal elongate fused paraethmoids curve at their posterior. The abocular side retrorbital vesicles are largest in volume only after the completion of normal eye migration. Factors involved in completion of normal metamorphosis and eye migration in flatfish affect chondral and dermal ossification signals in the ethmoid group, as well as remodeling of the mineralized frontal, a series of linked events not involving the entire neurocranium.
BACKGROUND: The present study was performed to investigate the effects of preoperative irradiation on distraction osteogenesis, as little is known about how preoperative irradiation delays distraction osteogenesis. METHODS: A single dose of irradiation was applied to the right rear legs of rabbits. This was followed by tibial lengthening at a rate of 0.5 mm/day, which was continued for 4 weeks. Bone regeneration was examined radiographically and histologically. RESULTS: In the irradiation group, the radiographs showed little regeneration during the elongation phase. During the maturation phase, the callus appeared slowly, and its formation was spotty. Furthermore, regeneration was not completed until the fourth week of the maturation period. Histological examination at the end of distraction showed a gap in the distraction consisting of loose connective tissue, with part of the fibrous tissue oriented longitudinally. Four weeks after completion of distraction, the major part of the radiolucent region consisted of cartilage. The spotty osteogenesis was identified as enchondral ossification. Immunohistochemical examination of the regeneration area revealed that the blood vessels were extremely localized, and that the level of expression of vascular endothelial growth factor (VEGF) in the osteoblasts was high. Microangiography showed that vascularization at the distracted sites was poor. Distraction osteogenesis was decreased markedly by preoperative irradiation in terms of both rate and process. The results suggested that most of the osteoprogenitor cells were damaged immediately after irradiation. The high level of VEGF in the osteoblasts and the enchondral ossification also suggested a hypoxic state in the distracted region. CONCLUSIONS: Preoperative irradiation interferes with distraction osteogenesis by inducing a state of poor angiogenesis.
Leptin, a 16-kD circulating hormone secreted mainly by white adipose tissue, is a product of the obese (ob) gene. Leptin acts on human marrow stromal cells to enhance differentiation into osteoblasts and inhibit differentiation into adipocytes. Leptin also inhibits bone formation through a hypothalamic relay. To obtain a better understanding of the potential role of leptin in bone formation, the localization of leptin in endochondral ossification was examined immunohistochemically. High expression of leptin was identified in hypertrophic chondrocytes in the vicinity of capillary blood vessels invading hypertrophic cartilage and in a number of osteoblasts of the primary spongiosa beneath the growth plate. The hypertrophic chondrocytes far from the blood vessels were negative for leptin. Moreover, we detected the production and secretion of leptin by a mouse osteoblast cell line (MC3T3-E1) and a mouse chondrocyte cell line (MCC-5) by RT-PCR, immunocytochemistry, and Western blotting. Leptin enhanced the proliferation, migration, tube formation, and matrix metalloproteinase-2 (MMP-2) activity of human endothelial cells (HUVECs) in vitro. These findings suggest the possibility that leptin exerts its influence on endochondral ossification by regulating angiogenesis.