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At least 1,063 records · Page 59Linked to original sources
PubMed1998

Natriuretic peptide regulation of endochondral ossification. Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway.

The natriuretic peptide family consists of three structurally related endogenous ligands: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The biological actions of natriuretic peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The natriuretic peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-peptide GC-coupled natriuretic peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.

Animals↗
PubMed2000

Changes of matrilin forms during endochondral ossification. Molecular basis of oligomeric assembly.

To understand the molecular properties of matrilin-3, a newly discovered member of the novel extracellular matrix protein family, we cloned a MAT-3 cDNA from developing chicken sterna. Real time quantitative reverse-transcription polymerase chain reaction indicates that MAT-3 mRNA is mainly expressed in the proliferation zone of a growth plate. It is also expressed in the maturation zone, overlapping with that of the mature chondrocyte-abundant matrilin-1 mRNA. This suggests that matrilin-3 may self-assemble in the proliferation zone, in addition to its co-assembly with matrilin-1 during endochondral ossification. Transfection of a MAT-3 cDNA into COS-7 cells shows that MAT-3 predominantly forms a homotetramer but also a trimer and a dimer. Co-transfection of both MAT-3 and MAT-1 cDNAs results in three major matrilins as follows: (MAT-1)(3), (MAT-3)(4), and (MAT-1)(2)(MAT-3)(2). Thus matrilin-3 may assemble into both homotypic and heterotypic oligomers. Our analysis shows that the assembly of MAT-3 does not depend on the number of epidermal growth factor repeats within the molecule, but the presence of Cys(412) and Cys(414) within the coiled-coil domain, which form covalent disulfide linkage responsible for both homo-oligomerization of MAT-3 and hetero-oligomerization of MAT-3 and MAT-1. Our data suggest that the varying synthetic levels of matrilins in different zones of a growth plate may result in a change of matrilin oligomeric forms during endochondral ossification.

Animals↗
PubMed1999

Matrix GLA protein is a developmental regulator of chondrocyte mineralization and, when constitutively expressed, blocks endochondral and intramembranous ossification in the limb.

Matrix GLA protein (MGP), a gamma-carboxyglutamic acid (GLA)-rich, vitamin K-dependent and apatite-binding protein, is a regulator of hypertrophic cartilage mineralization during development. However, MGP is produced by both hypertrophic and immature chondrocytes, suggesting that MGP's role in mineralization is cell stage-dependent, and that MGP may have other roles in immature cells. It is also unclear whether MGP regulates the quantity of mineral or mineral nature and quality as well. To address these issues, we determined the effects of manipulations of MGP synthesis and expression in (a) immature and hypertrophic chondrocyte cultures and (b) the chick limb bud in vivo. The two chondrocyte cultures displayed comparable levels of MGP gene expression. Yet, treatment with warfarin, a gamma-carboxylase inhibitor and vitamin K antagonist, triggered mineralization in hypertrophic but not immature cultures. Warfarin effects on mineralization were highly selective, were accompanied by no appreciable changes in MGP expression, alkaline phosphatase activity, or cell number, and were counteracted by vitamin K cotreatment. Scanning electron microscopy, x-ray microanalysis, and Fourier-transform infrared spectroscopy revealed that mineral forming in control and warfarin-treated hypertrophic cell cultures was similar and represented stoichiometric apatite. Virally driven MGP overexpression in cultured chondrocytes greatly decreased mineralization. Surprisingly, MGP overexpression in the developing limb not only inhibited cartilage mineralization, but also delayed chondrocyte maturation and blocked endochondral ossification and formation of a diaphyseal intramembranous bone collar. The results show that MGP is a powerful but developmentally regulated inhibitor of cartilage mineralization, controls mineral quantity but not type, and appears to have a previously unsuspected role in regulating chondrocyte maturation and ossification processes.

1-Carboxyglutamic Acid↗
PubMed2000

Connexin43 deficiency causes delayed ossification, craniofacial abnormalities, and osteoblast dysfunction.

Connexin(Cx)43 is the major gap junction protein present in osteoblasts. We have shown that overexpression of Cx45 in osteoblasts expressing endogenous Cx43 leads to decreased cell-cell communication (Koval, M., S.T. Geist, E.M. Westphale, A.E. Kemendy, R. Civitelli, E.C. Beyer, and T.H. Steinberg. 1995. J. Cell Biol. 130:987-995) and transcriptional downregulation of several osteoblastic differentiation markers (Lecanda, F., D.A. Towler, K. Ziambaras, S.-L. Cheng, M. Koval, T.H. Steinberg, and R. Civitelli. 1998. Mol. Biol. Cell 9:2249-2258). Here, using the Cx43-null mouse model, we determined whether genetic deficiency of Cx43 affects skeletal development in vivo. Both intramembranous and endochondral ossification of the cranial vault were delayed in the mutant embryos, and cranial bones originating from migratory neural crest cells were also hypoplastic, leaving an open foramen at birth. Cx43-deficient animals also exhibited retarded ossification of the clavicles, ribs, vertebrae, and limbs, demonstrating that skeletal abnormalities are not restricted to a neural crest defect. However, the axial and appendicular skeleton of Cx43-null animals were essentially normal at birth. Cell to cell diffusion of calcein was poor among Cx43-deficient osteoblasts, whose differentiated phenotypic profile and mineralization potential were greatly impaired, compared with wild-type cells. Therefore, in addition to the reported neural crest cell defect, lack of Cx43 also causes a generalized osteoblast dysfunction, leading to delayed mineralization and skull abnormalities. Cell to cell signaling, mediated by Cx43 gap junctions, was critical for normal osteogenesis, craniofacial development, and osteoblastic function.

Animals↗
PubMed1984

A sex- and age-limited ossification pattern in human costal cartilages.

In our continuing development of a roentgenographic method of determining age, race, and sex of cadaveric material, an absolutely distinctive pattern of ossification of the costal cartilages in older women has been identified. This ossification pattern has been found only in women over the age of 50 years and largely is restricted to those over 60 (i.e., remotely postmenopausal). Not encountered in men, this age/sex distinctive pattern is found in about one-third of the adult female autopsy population. It consists of rounded, solitary, or coalescent ossified foci confined to the central portions of the costal cartilages. These foci do not extend to the perichondrium and only very rarely involve the peristernal junctions. When this x-ray pattern is present, the decedent can be identified as an elderly female with great certainty.

Adult↗
PubMed2000

Restrained chondrocyte proliferation and maturation with abnormal growth plate vascularization and ossification in human FGFR-3(G380R) transgenic mice.

Achondroplasia, the most common genetic form of human dwarfism, results from a point mutation (G380R) in the gene for fibroblast growth factor receptor 3 (FGFR-3). Heterozygotes for the mutation share disproportionate, proximal shortening of the limbs, mid-face hypoplasia and relative macrocephaly due to a failure in endochondral ossification. Here we have generated transgenic mice expressing the human mutant FGFR-3 under the transcriptional control of the mouse gene. Mice that are hemizygous for the mutant human gene display disproportionate dwarfism with skeletal phenotypes remarkably similar to those of human achondroplasia. Mice that are homozygous for the transgene suffer from a profound delay in skeletal development and die at birth, similar in that respect to humans homozygous for the achondroplasia mutant gene. Microscopic analysis of long bones demonstrates growth plate morphology compatible with that of human achondroplasia cases, sharing endochondral growth inhibition with restrained chondrocyte proliferation and maturation, penetration of ossification tufts and aberrant vascularization.

Animals↗
PubMed2003

Impaired neuronal migration and endochondral ossification in Pex7 knockout mice: a model for rhizomelic chondrodysplasia punctata.

Rhizomelic chondrodysplasia punctata is a human autosomal recessive disorder characterized by skeletal, eye and brain abnormalities. The disorder is caused by mutations in the PEX7 gene, which encodes the receptor for a class of peroxisomal matrix enzymes. We describe the generation and characterization of a Pex7 mouse knockout (Pex7(-/-)). Pex7(-/-) mice are born severely hypotonic and have a growth impairment. Mortality in Pex7(-/-) mice is highest in the perinatal period although some Pex7(-/-) mice survived beyond 18 months. Biochemically Pex7(-/-) mice display the abnormalities related to a Pex7 deficiency, i.e. a severe depletion of plasmalogens, impaired alpha-oxidation of phytanic acid and impaired beta-oxidation of very-long-chain fatty acids. In the intermediate zone of the developing cerebral cortex Pex7(-/-) mice have an increase in neuronal density. In vivo neuronal birthdating revealed that Pex7(-/-) mice have a delay in neuronal migration. Analysis of bone ossification in newborn Pex7(-/-) mice revealed a defect in ossification of distal bone elements of the limbs as well as parts of the skull and vertebrae. These findings demonstrate that Pex7 knockout mice provide an important model to study the role of peroxisomal functioning in the pathogenesis of the human disorder.

Acetyl-CoA C-Acetyltransferase↗
PubMed1987

Heterotopic ossification (myositis ossificans) in acquired immune deficiency syndrome. Detection by gallium scintigraphy.

A case of heterotopic ossification (myositis ossificans) secondary to the central nervous system complications of acquired immune deficiency syndrome (AIDS) is reported. Because of the overwhelming suspicion of infection in this patient, this diagnosis was not considered until a gallium scan revealed the typical findings of heterotopic ossification. Because of the increasing utilization of gallium imaging in the AIDS population, every imaging specialist should be aware of this potential disorder.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Heterotopic ossification: can early surgery be performed, with a positive bone scan?

It has been previously suggested that the surgical removal of areas of heterotopic ossification in patients with burns should be delayed until bone scans return to normal. The present study describes a patient who underwent surgical removal of heterotopic ossification from both elbows, 1 year after burn injury, with strongly positive bone scans, because of progressive ulnar nerve compression. Subsequently, 7 years after burn injury and 6 years after this surgery, the patient maintained an excellent range of motion in both elbows. At this time, his bone scans continue to be strongly positive. Didronel (Norwich Eaton, Norwich, N.Y.), a diphosphonate, may have played a role in this patient's recovery by decreasing bony deposition following surgery.

Adult↗
PubMed1997

Anterior decompression and fusion using bone grafts obtained from cervical vertebral bodies for ossification of the posterior longitudinal ligament of the cervical spine: technical note.

OBJECTIVE: To describe a surgical technique of anterior decompression and fusion using bone grafts obtained from cervical vertebral bodies with ossification of the posterior longitudinal ligament of the cervical spine. This technique seeks to avoid complications associated with an anterior approach of decompression and bone fusion, which widely uses autogenous bone from the iliac crest. METHODS: Forty patients with cervical myelopathy were studied. The ossified ligament was localized to one, two, three, four, five, six, and seven vertebral bodies in 10, 18, 5, 4, 1, 1, and 1 patients, respectively. The ossified area of all posterior longitudinal ligament was completely removed using microsurgical techniques, and 11 patients were operated on at one level, 21 at two levels, and 8 at three levels. RESULTS: The symptoms of all patients improved after the operation. Postoperative x-ray films showed solid bone fusion in all patients at a mean follow-up time of 3 years (range, 1-5.25 yr). Anterior angulation was found in one of eight patients (13%) who underwent three-level fusion. CONCLUSION: Two major advantages were as follows: 1) no complications related to the iliac donor site occurred, and 2) early mobilization of patients was possible with a soft cervical collar. Anterior decompression and fusion should be used for cases with ossification of up to three consecutive vertebrae needing either one- or two-level fusions.

Adult↗
PubMed2001

A murine osteosarcoma cell line with a potential to develop ossification upon transplantation.

An osteosarcoma cell line has been established from a soft tissue tumor that occurred spontaneously in a BALB / c mouse. This cell line showed ossification when transplanted into syngeneic mice. To examine the mechanism of bone formation, the expression of mRNAs for osteoblastic and chondroblastic markers and factors associated with ossification has been investigated. In culture, the cells exhibited a spindle shape in the growth phase, but had a polygonal shape in the stationary phase. Reverse transcription-polymerase chain reaction analysis showed that the cells expressed mRNAs for pro-alpha1(I) chain of type I collagen, alkaline phosphatase, osteopontin, osteocalcin, and core binding factor alpha1, suggesting differentiation into the stage of osteoblasts during the stationary phase. After transplantation, histological examination revealed small foci of pale blue material and basophilic networks that were scattered in the tumor tissues at one week. The former stained positive with alcian blue, suggesting a chondroid matrix. Pro-alpha1(II) chain of type II collagen mRNA was expressed at one week. A large part of tumors at two and three weeks consisted of basophilic networks, which stained positive via von Kossa's method, indicating a calcified woven bone. In situ hybridization analysis showed strong expression of osteopontin and osteocalcin mRNAs in tumor cells surrounding the bone matrix. Bone morphogenetic protein-6 and -7 mRNAs were detected in transplanted tumors, but not in cultured cells. These results suggest that the cell line has the properties of an osteoblastic lineage when cultured in vitro and has an ossifying ability through endochondral bone formation processes when transplanted in vivo.

Alkaline Phosphatase↗
PubMed1998

Ossification and growth rates of the limb long bones during the prehatching period in the quail (Coturnix coturnix japonica).

The timing of ossification and the growth of six long bones of the prehatching period in the quail was studied. Ninety-nine quail eggs were incubated and in total nine fetuses were selected daily from the sixth to the sixteenth day of incubation. The fetuses were stained with alizarine and alcian blue double colouration. The fetuses were studied under the stereoscopic microscope and linear measurements were obtained from the humerus, ulna, radius, femur, tibia and fibula. The first appearance of the primary ossification centres in the diaphysis of the studied bones was found to occur between the sixth and the seventh day of incubation. Different growth patterns between the bones of the leg and of the wing were observed. Humerus and tibia showed the greatest growth rate while the radius and fibula showed the lowest.

Animals↗
PubMedDate not supplied

Incomplete ossification of the humeral condyle in spaniels.

An evaluation of 157 dogs with humeral fractures was performed. Cocker spaniels were more likely to have humeral condylar fractures (HCFs) than other breeds (P < .001). Male cocker spaniels were at increased risk (P < .001). Cocker spaniels had more bilateral HCFs than other breeds of dogs (P < .001). Eighteen dogs (17 purebred spaniels and 1 crossbred spaniel) with HCFs of unknown cause or occurring with normal activity were further studied, using radiography of their humeral condyle bilaterally (n = 18), computed tomography (n = 3), biopsy (n = 2), bone scintigraphy (n = 2), and genetic evaluation (n = 8). Fourteen of these 18 dogs had a nonfractured contralateral condyle. Twelve (86%) of the 14 nonfractured humeral condyles had a radiolucent line within the center of the condyle, 13 (93%) had radiographic signs of degenerative joint disease and an abnormal medial coronoid process, and six (43%) had periosteal proliferation involving the lateral epicondyle. Examination of biopsy samples from the fracture sites of two cocker spaniels showed fibrous tissue present at the fracture surfaces. The results of this study suggest an association between incomplete ossification of the humeral condyle in cocker spaniels and Brittany spaniels and a high prevalence of HCFs. Eight affected cocker spaniels with available pedigree information were found to be genetically related, suggesting that incomplete ossification of the humeral condyle may be a genetic disease with a recessive mode of inheritance.

Animals↗
PubMed1990

Ossification in nude mice. 1. Macroscopical study.

Ossification was studied in cleared fetuses, newborns, 1- and 6-week-old nu/nu and nu/+ mice of the B 10 LP background. The same ossification pattern was observed in nu/nu and nu/+ in the embryonal period as well as in newborn animals and mice aged 1 or 6 weeks. On the other hand, 6-week-old nu/nu mice exhibited a lower X-ray density of the skeleton and a lower thickness of the proximal tibial growth plate than 6-week-old nu/+ litter mates. The results indicate the influence of postnatal factors on the skeletal development of nu/nu mice.

Animals↗
PubMedDate not supplied

Incomplete ossification of the humeral condyle in Vietnamese pot-bellied pigs.

The purpose of this study was to evaluate the occurrence of humeral condylar fractures in Vietnamese pot-bellied pigs and to postulate a possible predisposing cause for these fractures. Thirteen Vietnamese pot-bellied pigs (Group A) were evaluated over an eight year period (1990-1998), each with a history of either a unilateral or bilateral forelimb lameness. The cause of lameness was localized to the elbow region. Of the thirteen pigs, twenty-one elbows were evaluated radiographically. Pigs ranged in age from six months to four years old. All pigs over the age of seven months showed radiographic evidence of elbow degenerative joint disease. Fractures involving the medial aspect of the humeral condyle were identified in 8/21 studies (38%). A well-defined linear intracondylar articular lucency was identified in 7/21 studies (33%) on the craniocaudal projection. The site of this lucency corresponded to the location of the articular component of the fractures seen involving the humeral condyle. The elbows of five pot-bellied pigs with no known history of forelimb lameness or trauma (Group B) were evaluated radiographically following euthanasia. All five pigs were of unknown age and gender. An intracondylar vertical linear lucency was identified bilaterally in three pigs (60%). Concurrent degenerative joint disease was present in all instances. The remaining two pigs were radiographically normal. Computed tomography of the elbows was performed in one affected pig from Group B. The radiographic findings in this pig were verified. Histopathology of the right elbow of this affected pig was diagnostic for incomplete endochondral ossification of the humeral condyle. A similar condition involving the humeral condyle has been previously described in Cocker and Brittany Spaniels. These canine breeds also have a high incidence of humeral condylar fractures. It is postulated that Vietnamese pot-bellied pigs are similarly prone to humeral condylar fractures, even in the absence of known trauma, due to incomplete ossification of the humeral condyle.

Animals↗
PubMed2005

Metaplastic ossification of a cervical sialocoele in a dog.

Metaplastic ossification of a long-standing cervical sialocoele was identified in a 2-year-old male Hellenic Hound dog. Diagnosis was based upon history, clinical findings, paracentesis and histopathology. Trauma or chronic inflammation of the mandibular gland/duct complex were the most probable causes of the ossification. Surgical excision of the ossified mass, as well as of mandibular and sublingual salivary glands/ducts of the affected side, resulted in clinical remission.

Animals↗
PubMed2002

Chondromodulin I is dispensable during enchondral ossification and eye development.

Chondromodulin I (chm-I), a type II transmembrane protein, is highly expressed in the avascular zones of cartilage but is downregulated in the hypertrophic region, which is invaded by blood vessels during enchondral ossification. In vitro and in vivo assays with the purified protein have shown chondrocyte-modulating and angiogenesis-inhibiting functions. To investigate chm-I function in vivo, we generated transgenic mice lacking chm-I mRNA and protein. Null mice are viable and fertile and show no morphological changes. No abnormalities in vascular invasion and cartilage development were detectable. No evidence was found for a compensating function of tendin, a recently published homologue highly expressed in tendons and also, at low levels, in cartilage. Furthermore, no differences in the expression of other angiogenic or antiangiogenic factors such as transforming growth factor beta1 (TGF-beta1), TGF-beta2, TGF-beta3, fibroblast growth factor 2, and vascular endothelial growth factor were found. The surprising lack of phenotype in the chm-I-deficient mice suggests either a different function for chm-I in vivo than has been proposed or compensatory changes in uninvestigated angiogenic or angiogenesis-inhibiting factors. Further analysis using double-knockout technology will be necessary to analyze the function of chm-I in the complex process of enchondral ossification.

Alleles↗
PubMed1967

Ossification in the sternum as a means of assessing skeletal age.

The centres of ossification in the sternum were investigated to determine whether there was any correlation between ossification in the sternum and chronological age. But this proved to be of no value in assessing skeletal age, although it may be of use in assessing skeletal maturity for pathological or forensic purposes.

Age Determination by Skeleton↗