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At least 415 records · Page 23Linked to original sources
PubMed2004

Expression of the Ellis-van Creveld (Evc) gene in the rat tibial growth plate.

Ellis-van Creveld (EvC) syndrome is an autosomal recessive chondrodysplasia characterized by short limbs, postaxial polydactyly, natal teeth, and dysplastic nails. The Ellis-van Creveld (EVC) gene, which is mutated in patients with EvC syndrome, has been identified by positional cloning. However, the physiological roles of the EVC gene have not been elucidated. Histopathological analyses of EvC syndrome have shown disturbed chondrocytic phenotypes during cartilage development. We therefore postulated that the EVC gene is a critical factor for chondrocytes during endochondral ossification. The present study focuses on the relationship between the Evc gene and chondrocytes, and examines Evc gene expression in the rat tibial growth plate at the mRNA and protein levels. Evc mRNA in tibial epiphyseal cartilage was expressed at postnatal day (P) 1, P28, and P56 by RT-PCR. Immunohistochemical analyses localized the Evc protein mainly in prehypertrophic and hypertrophic chondrocytes of the epiphyseal growth plate in the tibia during the embryonic and postnatal periods. Evc mRNA was also detected in prehypertrophic and hypertrophic chondrocytes by in situ hybridization. These results indicate that the Evc gene functions mainly in the prehypertrophic and hypertrophic chondrocytes of the epiphyseal growth plate. The data presented here are important for future studies of the underlying mechanism of chondrodysplasia in EvC syndrome.

Animals↗
PubMed2005

Localization of matrix metalloproteinases, (MMPs) their tissue inhibitors, and vascular endothelial growth factor (VEGF) in growth plates of children and adolescents indicates a role for MMPs in human postnatal growth and skeletal maturation.

Numerous studies have focused on the expression, regulation, and biological significance of matrix metalloproteinases (MMPs) in the growth plate. Findings in mouse knockout models and in vitro data from various species indicate that MMPs not only degrade extracellular matrix components but may regulate the activity of local growth factors. In this study we investigated the presence, distribution, and activity of various MMPs and inhibitors, tissue transglutaminase (tTG or TG2) and vascular endothelial growth factor (VEGF) in the human child and adolescent growth plates by means of immunohistochemistry and gelatin zymography. Tissue was derived during orthopedic surgery (epiphysiodesis) in two prepubertal and four pubertal patients.MMP-2 and MMP-14 were present in reserve cell chondrocytes. MMP-14 was the most prominent MMP within all zones of the growth plate including proliferating chondrocytes. MMP-1 and MMP-13 (collagenases 1 and 3), MMP-9 (gelatinases B), MMP-10, and MMP-11 (stromelysins) and VEGF were positive in hypertrophic chondrocytes and osteoblasts. MMP-2 showed the same expression pattern but was negative in osteoblasts. Osteoclasts stained positive for MMP-9, MMP-2, and TG2. Tissue inhibitor of MMP (TIMP)-1 was present in all zones of the growth plate, osteoblasts, and osteoclasts; TIMP-2 was found in hypertrophic chondrocytes and osteoblasts. In summary, the presence of MMPs, TIMPs, TG2, and VEGF in our study indicated that the MMPs are relevant in growth plate physiology during the postnatal period in humans. The specific location of MMP expression within the growth plate may be the basis for further studies on the role of MMPs in the local regulation of chondrocyte differentiation, proliferation, and ossification at the chondroosseus junction.

Adolescent↗
PubMed1997

Histopathological study on bone changes induced by recombinant granulocyte colony-stimulating factor in rats.

Histopathological bone changes were examined in growing rats intravenously administered with high doses (100 and 1000 micrograms/kg/day) of recombinant human granulocyte colony-stimulating factor (rG-CSF) for 28 days. The changes were observed in the region where physiological bone resorption actively occurs in the growth phase, that is the trabeculae of metaphyseal spongy bone and the endosteum region of diaphyseal compact bone. Histologically, the changes involved accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification. While osteoclastic bone resorption was observed in almost all lesions, about half of which were accompanied by osteogenesis. Bone changes which appeared after administration of rG-CSF were characterized by frequent occurrence at the site of highly osteoclastic activity and by initial osteoclastic resorption followed by osteogenesis due to intramembranous ossification. These results suggest that the main action of rG-CSF on bone may be an acceleration of osteoclastic bone resorption.

Animals↗
PubMed2002

Effects of chemotherapy on bone metabolism and skeletal growth.

In recent years there has been a significant increase in both acute and chronic toxicity associated with the more successful but now highly intensive chemotherapy (CT) regimens used to treat childhood cancers. The incidence of childhood cancers coincides with periods of rapid skeletal development. Consequently, short stature and osteoporosis are important long-term effects in adult survivors. Clinical data indicate that the effects of CT, including glucocorticoids, on final height are due to direct effects of these drugs on the skeleton. The multiple modes of action of CT drugs suggest a complex and diverse influence on chondrocytes, extracellular matrix and bone cells. However, only limited data demonstrate these direct effects on the proliferative capacity of growth plate chondrocytes and on key steps of endochondral ossification, the multistep process that determines rate and extent of long bone growth. Endochondral ossification requires coordinated maturation, proliferation and differentiation of growth plate chondrocytes leading to hypertrophic cells which eventually undergo apoptosis to leave a cartilaginous scaffold that is mineralized prior to the laying down of new bone. Disruption of the physiological cellular activity of growth plate chondrocytes and/or bone cells result in skeletal growth disturbances. Thus, CT drugs which disrupt normal cell division may manifest their effects on the growth plate as either a reduction in cell number and/or the loss of functional integrity of extracellular matrix. Histological and cell kinetic studies, using in vivo and in vitro models of long bone growth, are essential to increase our understanding of the cellular mechanisms involved and to finally determine how the individual growth potential might be maintained during treatment for childhood cancers.

Antineoplastic Agents↗
PubMed1989

Adolescent tibia vara.

Adolescent tibia vara is less common and less well described when compared to infantile tibia vara. Yet, the two share a significant number of features related to their epidemiology and histology. The two diseases differ most in their radiographic appearance. It does not, however, necessarily follow that their etiologies cannot be similar. By its epidemiology and histology, adolescent tibia vara appears to be related to repetitive trauma in the form of abnormal force directed on the medial tibial growth plate due to obesity, the adolescent growth spurt, or residual, incompletely corrected physiologic varus. Such forces may give growth plate suppression by the Heuter Volkman principle similar to what is thought to occur in infantile tibia vara. In the infant, this results in typical radiologic findings related to an epiphyseal ossification center which is cartilagenous and moldable and results in progressive medial wedging. In the adolescent, however, this ossification center is bony and, therefore, will not deform under stress. The growth plate, however, still responds with decreased growth resulting in varus deformity. Thus, adolescent tibia vara, by definition not related to trauma or infection, may in fact reflect the same pathologic process at work as in infantile tibia vara.

Child↗
PubMed1983

Unusual intrauterine objects: potential pitfalls in ultrasonographic identification.

Three cases of echogenic objects in the uterine cavity are reported. These objects had ultrasonographic characteristics of contraceptive intrauterine devices (IUDs) and, in the absence of patients' medical histories, would almost certainly have been wrongly identified as such. The authors demonstrate that noncontraceptive intrauterine objects can mimic IUDs.

Adult↗
PubMed1984

Induced osteogenesis--the biological principle and clinical applications.

Complex orthopedic and craniofacial surgical procedures have stimulated renewed interest in the physiology of bone grafting. The experimental and clinical evidence that a nonvital implant can stimulate local host cells to become bone-forming cells (osteoinduction) is reviewed. Studies of induced osteogenesis were derived from old clinical observations of heterotopic ossification in scars and muscle. When demineralized bone is placed within soft tissues of a rat, a remarkable sequence of endochondral ossification occurs. In contrast, mineral-containing bone particles stimulate obligatory resorption by host mono- and multinucleated cells. The biochemical, endocrine, and physicochemical aspects of induced osteogenesis are actively being investigated. Present understanding of the mechanism of bone induction is discussed along with descriptions of preliminary clinical trials with allogeneic demineralized implants.

Abnormalities, Multiple↗
PubMed1989

Postoperative instability of cervical OPLL and cervical radiculomyelopathy.

The presence of cervical spine instability with respect to preoperative and postoperative changes in angular, horizontal, and rotational displacement of the vertebral body were studied. With the anterior approach, the instability in the remaining unfused segments, and their relation to the kyphotic or lordotic fused segment were studied. With the posterior approach, postoperative ROM (range of motion) could be better maintained, and horizontal displacement was improved in more cases by laminoplasty compared with laminectomy. With the anterior approach, the compensatory function for the loss of motion of the segments resulting from fusion was most remarkable at the levels of C2-3 and C6-7. In the alignment of the anterior fused segments, it appears important that the physiologic lordotic position be maintained.

Adult↗
PubMed1975

Development of femoral head to the rat from calcification to ossification.

The development of the epiphysis of the femoral head from calcification to ossification was investigated in 50 rats of Wistar strain from an age of 10 to 63 days using radiography and histology. The first deposition of calcium in the cartilage appeared in the central portion of the epiphysis at an age of about 21 days. The region of calcification gradually expanded toward the periphery and after about 3 weeks it occupied the entire epiphysis except for the periphery. After completion of calcification ossification began in the lateral part of the epiphysis at the earliest at an age of 6 weeks. The onset of ossification was characterized by disintegration of hypertrophied cartilage cells and formation of bone trabeculae accompanied by vascular invasion from the lateral side.

Animals↗
PubMed1986

[A study of the effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on reproduction. II. Its teratogenicity in rats and rabbits].

This paper describes the embryotoxicity and teratogenic effects of (2"R)-4'-O-Tetrahydropyranyladriamycin (THP). The drug was administered intravenously to female rats at 0.01, 0.03, 0.1 or 0.3 mg/kg daily from day 7 to day 17 of pregnancy and to female rabbits at 0.01, 0.05 or 0.1 mg/kg daily from day 6 to day 18 of pregnancy. Results were summarized as follows. Rats THP, at the highest dose of 0.3 mg/kg, decreased body weight gains of pregnant females. This dose caused a decrease in body weights of fetuses, tendencies to increase the rate of death of fetuses or of resorption, an increase in the number of lumbar vertebrae and a delayed ossification of forelimbs of fetuses. Other parameters were not affected by THP at any dose levels. At any dose levels, THP did not produce external, visceral or skeletal malformations in the offspring (F1), nor did it affect the development, physiological functions, behavior, mating, fertility or pregnancy of the offspring. However, at the highest dose level, THP decreased the weight of testes of the offspring. The results suggest that the maximum "no effect" dose level of THP to pregnant females and offspring is 0.1 mg/kg/day intravenously. Rabbits The highest dose of THP, 0.1 mg/kg, decreased the consumption of food and water by pregnant females, but at any dose levels, it did not affect their body weight gain. THP did not cause teratological effects such as external malformation or visceral and skeletal anomalies in the fetuses at any dose levels tested. The results suggest that the maximum "no effect" dose of THP is 0.05 mg/kg/day intravenously to pregnant females and above 0.1 mg/kg/day intravenously to fetuses.

Abnormalities, Drug-Induced↗
PubMed1997

OP-1 (BMP-7) affects mRNA expression of type I, II, X collagen, and matrix Gla protein in ossifying long bones in vitro.

In long bone development, a regulating role of OP-1 is suggested by the local correlated expression of both OP-1 ligand and OP-1 binding receptors in developing mouse hind limbs. OP-1 is expressed in the interdigital mesenchyme, whereas OP-1 binding receptors are found in the bordering perichondrium, and both OP-1 ligand and receptors are present in the zone of (pre)hypertrophic chondrocytes. We investigated the role of OP-1 in long bone development experimentally by treating organ cultures of embryonic mouse metatarsals with rhOP-1. The mRNA expression patterns of type I, II, X collagen, and matrix Gla protein (MGP) were studied using in situ hybridization and cell proliferation using [3H]thymidine and BrdU labeling. In the epiphyseal perichondrium, treatment with 40 ng/ml OP-1 enhanced cell proliferation after day 2, while 6-day treatment caused a shift in expression from type I collagen to type II collagen mRNA. This supports previous histochemical findings that OP-1 induced the transition of perichondrium into cartilage. In the center of the rudiment, OP-1 inhibited the expression of type X collagen mRNA, indicating inhibition of chondrocyte hypertrophy. An arrest of differentiation at the (pre)hypertrophic chondrocyte stage was also indicated by the large area of cells expressing MGP mRNA in the OP-1-treated rudiments. We conclude that OP-1 affected the expression of marker genes of chondrocyte differentiation by acting on two steps in endochondral ossification. First, cell proliferation was enhanced, particularly so in the perichondrium where cells started to express the chondrocyte phenotype. Second, the terminal differentiation of mature chondrocytes into hypertrophic chondrocytes was inhibited. These results, combined with the known pattern of OP-1 ligand and BMP receptor expression in the embryo, suggest that OP-1 plays a local role in the cascade of events during endochondral ossification.

Animals↗
PubMed1995

Matrix metalloproteinases and TIMP-1 localization at sites of osteogenesis in the craniofacial region of the rabbit embryo.

BACKGROUND: The matrix metalloproteinases (MMPs) are a family of closely related enzymes, the principal members being the collagenases, gelatinases, and stromelysins. They are synthesized and secreted by connective tissue cells and are capable of degrading all the components of connective tissue matrices at physiological pH. METHODS: Patterns of synthesis and distribution of MMPs and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), are documented in the craniofacial region at sites of bone formation during both intramembranous (e.g., calvaria, maxilla, and mandible) and endochondral ossification (e.g., cartilaginous cranial base and synchondroses) using indirect immunolocalization. RESULTS: MMPs and TIMP-1 were detected both as bright intracellular accumulations, indicating active synthesis, and as diffuse matrix-bound extracellular deposits. Gelatinase-A had an extensive distribution in osteogenic tissues and was detected both in cells of the periosteum and spongiosum and as extracellular deposits in the osteoid layer of newly formed bone. In addition, gelatinase-AB synthesis was detected in osteoclasts. All regions of the early cartilaginous cranial base produced MMPs and TIMP-1, and synthesis continued in the established synchondrosis. MMPs and TIMP-1 were also documented in early tooth germs and in Meckel's cartilage. CONCLUSIONS: These data document a prominent role for MMPs, and in particular gelatinase-A, in mediating matrix degradation during osteogenesis. Their detection in tooth germs and Meckel's cartilage further indicates a role for MMPs and TIMP-1 in matrix turnover during morphogenesis.

Animals↗
PubMed2005

Immunohistochemical characteristics of developing mandibular angle in fetal mice.

Mouse mandibular angle development started as a coagulation of mesemchymal cells on the 15(th) fetal day. On the 16(th )fetal day, cells of the central portion of the cell coagulation showed metachromasia to toluidine blue, and type 2 collagen positive chondrocytes were immunohistochemically detected. After the 17(th) fetal day, cartilaginous osteogenesis occurred with invasion of capillaries. At the same stage, membranous (perichondral) ossification occurred in the periphery of the chondrocyte mass. These proliferating chondrocytes showed positive reactions to type 2 collagen, type 1 collagen and osteopontin. These results suggest that the characteristics of mandibular angular cartilage are slightly different from those of normal physiological articular cartilage.

Animals↗
PubMed1989

Influence of nicotine and caffeine on skeletal development in the rat.

The effects of nicotine and caffeine at dose levels approximating human consumption on skeletal development was investigated in Sprague-Dawley rats. One group of animals received nicotine administered subcutaneously by an Alzet miniosmotic pump from gestational d 6 through 12 (25 mg over 7 d; rate 149 micrograms/h). Control animals received physiological saline in a similar manner. A2. group received a single intravenous injection of caffeine (25 mg/kg) on gestational d 6. Control animals were treated with physiological saline. A further group received both nicotine and caffeine on gestational d 6 as described for the 2 previous groups. Evaluation of the fetal skeletal system on gestational d 20 revealed a significant decrease in the number of complete sternal ossification centers, as well as delays in the ossification of the skull and face, following combined nicotine and caffeine treatment. Other skeletal anomalies and variations were frequently observed, but their incidences were not significantly increased in any of the treatment groups, compared to the corresponding controls. A coteratogenic effect is evident between nicotine and caffeine on account of the increased incidence of delayed and abnormal skeletal development.

Animals↗
PubMed2005

Leptin regulates chondrocyte differentiation and matrix maturation during endochondral ossification.

Leptin has been suggested to mediate a variety of actions, including bone development, via its ubiquitously expressed receptor (Ob-Rb). In this study, we investigated the role of leptin in endochondral ossification at the growth plate. The growth plates of wild-type and ob/ob mice were analyzed. Effects of leptin on chondrocyte gene expression, cell cycle, apoptosis and matrix mineralization were assessed using primary chondrocyte culture and the ATDC5 cell differentiation culture system. Immunohistochemistry and in situ hybridization showed that leptin was localized in prehypertrophic chondrocytes in normal mice and that Ob-Rb was localized in hypertrophic chondrocytes in normal and ob/ob mice. Growth plates of ob/ob mice were more fragile than those of wild-type mice in a mechanical test and were broken easily at the chondro-osseous junction. The growth plates of ob/ob mice showed disturbed columnar structure, decreased type X collagen expression, less organized collagen fibril arrangement, increased apoptosis and premature mineralization. Leptin administration in ob/ob mice led to an increase in femoral and humeral lengths and decrease in the proportional length of the calcified hypertrophic zone to the whole hypertrophic zone. In primary chondrocyte culture, the matrix mineralization in ob/ob chondrocytes was stronger than that of wild-type mice; this mineralization in both types of mice was abolished by the addition of exogenous leptin (10 ng/ml). During ATDC5 cell differentiation culture, exogenous leptin at a concentration of 1-10 ng/ml (equivalent to the normal serum concentration of leptin) altered type X collagen mRNA expression and suppressed apoptosis, cell growth and matrix calcification. In conclusion, we demonstrated that leptin modulates several events associated with terminal differentiation of chondrocytes. Our finding that the growth plates of ob/ob mice were fragile implies a disturbance in the differentiation/maturation process of growth plates due to depletion of leptin signaling in ob/ob mice. These findings suggest that peripheral leptin signaling plays an essential role in endochondral ossification at the growth plate.

Animals↗
PubMed2004

Matrix remodeling during endochondral ossification.

Endochondral ossification, the process by which most of the skeleton is formed, is a powerful system for studying various aspects of the biological response to degraded extracellular matrix (ECM). In addition, the dependence of endochondral ossification upon neovascularization and continuous ECM remodeling provides a good model for studying the role of the matrix metalloproteases (MMPs) not only as simple effectors of ECM degradation but also as regulators of active signal-inducers for the initiation of endochondral ossification. The daunting task of elucidating their specific role during endochondral ossification has been facilitated by the development of mice deficient for various members of this family. Here, we discuss the ECM and its remodeling as one level of molecular regulation for the process of endochondral ossification, with special attention to the MMPs.

Animals↗
PubMed2000

[Neurology in Paris hospitals, particularly the Salpêtrière before Charcot: Rostan on brain softening].

In the beginning of the 19th century, many studies were devoted to the diseases of the nervous system in France, long before the work of Charcot. The researches of Léon Rostan on the cerebral softening (1819, 1823) were based on the anatomoclinic method developed by the School of Paris whose most famous representatives were Corvisart and Laennec for the study of heart and lung diseases. The researches of Rostan were performed in the Salpêtrière hospital which was, at this time, an hospice for old women. Rostan was appointed Inspector of the Health service in the Salpêtrière hospital in 1812 then Head of a department in 1818. He was 28 year old when he published his book "Researches on the cerebral softening" in 1819. Rostan was the first to describe the spontaneous cerebral softening as a special anatomoclinic entity distinct from encephalitis and apoplexy. He compared this entity to the senile gangrene and stated that it was related to the ossification of cerebral arteries. He described the pathologic features of the brain softening and also its clinical symptomatology in opposition to that of apoplexy. The concept of brain softening according to Rostan was harshly fought by the followers of the Broussais's physiological medicine (from Lallemand, 1830 to Calmeil, 1859) who claimed that all brain softenings were due to the inflammation process and thus should be described as encephalitis. In opposite, the ideas of Rostan were accepted and developed by others such as Carswell in England (1835), Abercrombie in Scotland (1836) and Andral in France (1827, 1840). These authors agreed that some type of cerebral softening was related to a disease of the arterial system. Nevertheless, the modern concept of brain softening was not definitively accepted before the description of the thromboembolic mechanisms by Virchow in Germany (1856) with the help of the microscope, and the anatomoclinic studies of Proust, Laborde and Prevost and Cottard in France (1866). The book of Rostan was dedicated to the "Conseil Général des Hospices" which was created in 1801 to unify the administration of the hospitals in Paris and became the "Administration Générale de l'Assistance Publique à Paris" in 1849. One hundred and fifty years after its publication, the work of Léon Rostan was outstanding by its modernity of the form as well as the substance.

Cerebrovascular Circulation↗