共查询到20条相似文献,搜索用时 31 毫秒
1.
Noriyoshi Kurihara Hua Zhou Sakamuri V Reddy Veronica Garcia Palacios Mark A Subler David W Dempster Jolene J Windle G David Roodman 《Journal of bone and mineral research》2006,21(3):446-455
We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. INTRODUCTION: Paget's disease (PD) of bone is the second most common bone disease. Both genetic and viral factors have been implicated in its pathogenesis, but their exact roles in vivo are unclear. We previously reported that transfection of normal human osteoclast (OCL) precursors with the measles virus nucleocapsid (MVNP) or measles virus (MV) infection of bone marrow cells from transgenic mice expressing a MV receptor results in formation of pagetic-like OCLs. MATERIALS AND METHODS: Based on these in vitro studies, we determined if the MVNP gene from either an Edmonston-related strain of MV or a MVNP gene sequence derived from a patient with PD (P-MVNP), when targeted to cells in the OCL lineage of transgenic mice with the TRACP promoter (TRACP/MVNP mice), induced changes in bone similar to those found in PD. RESULTS: Bone marrow culture studies and histomorphometric analysis of bones from these mice showed that their OCLs displayed many of the features of pagetic OCLs and that they developed bone lesions that were similar to those in patients with PD. Furthermore, IL-6 seemed to be required for the development of the pagetic phenotype in OCLs from TRACP/MVNP mice. CONCLUSIONS: These results show that persistent expression of the MVNP gene in cells of the OCL lineage can induce pagetic-like bone lesions in vivo. 相似文献
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Dorit Naot Usha Bava Brya Matthews Karen E Callon Gregory D Gamble Michael Black Sarah Song Rocco P Pitto Tim Cundy Jill Cornish Ian R Reid 《Journal of bone and mineral research》2007,22(2):298-309
Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease. 相似文献
9.
Contribution of modern research technics to the identification of a virus in Paget's disease of bone
A Rebel M F Basle J G Fournier W C Russel 《Bulletin de l'Association des anatomistes》1986,70(209):15-20
The morphological resemblance between osteoclast inclusions in Paget's bone disease and viral structures has encouraged new research with immunocytologic methods and In Situ hybridization. Paramyxovirus antigens of measles virus and respiratory syncitial virus were detected in pagetic osteoclasts using polyclonal antibodies. Paramyxovirus antigens of measles virus, simian virus (SV 5) and human parainfluenza virus (PF 3) were demonstrated using monoclonal and monospecific polyclonal antibodies. Measles virus nucleotide sequences were detected in pagetic osteoclasts by In Situ hybridization with a 3H labelled cDNA probe specific for measles nucleocapsid protein. However, the same probe also hybridized with several types of mononucleated cells suggesting a wide host range for measles virus genomic information. Apparently, this viral information is translated only in the osteoclasts. The link between the presence of viral information in pagetic bone tissue cells and Paget's disease itself still awaits elucidation. 相似文献
10.
Evidence for both respiratory syncytial virus and measles virus antigens in the osteoclasts of patients with Paget's disease of bone 总被引:4,自引:0,他引:4
B G Mills F R Singer L P Weiner S C Suffin E Stabile P Holst 《Clinical orthopaedics and related research》1984,(183):303-311
Recent ultrastructural and immunohistochemical evidence supports the hypothesis that Paget's disease of bone is a slow viral infection of the Paramyxoviridae family. Conflicting evidence for the presence of respiratory syncytial virus (RSV), a pneumovirus, or measles, a morbillivirus, has been reported. By the indirect fluorescent antibody assay, four RSV antisera were compared with four measles antisera on serial sections of pagetic bone or replicate coverslips of cells from pagetic bone grown in culture from 30 patients. Results produced positive immunofluorescence for RSV in 28 of 29 patients and positive immunofluorescence for measles in 11 of 22 patients. Of the 20 patients from whom comparable samples could be tested for antigens, 11 were found to harbor both antigens. These studies support the hypothesis that Paget's disease of bone is a slow viral infection of the Paramyxoviridae family more closely related to the pneumoviruses than the morbilliviruses. 相似文献
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G J R Cook G M Blake P K Marsden B Cronin I Fogelman 《Journal of bone and mineral research》2002,17(5):854-859
The purpose of this study was to quantify indices of regional bone metabolism in Paget's disease and to compare these indices with normal bone using dynamic 18F-fluoride positron emission tomography (PET). Seven patients with vertebral Paget's disease had 1 h dynamic 18F-fluoride PET scans performed. The scans included a diseased vertebra and an adjacent normal vertebra. Arterial plasma input functions were also measured. A three-compartment, four-parameter model was used with nonlinear regression analysis to estimate bone kinetic variables. Compared with normal bone, pagetic bone demonstrated higher values of plasma clearance to bone mineral (Ki; 1.03 x 10(-1) vs. 0.36 x 10(-1) ml/min per milliliter; p = 0.018) and clearance to total bone tissue (K1; 2.38 x 10(-1) vs. 1.25 x 10(-1) ml/min per milliliter; p = 0.018), reflecting increased mineralization and blood flow, respectively. Release of 18F-fluoride from bone mineral (k4) was lower in pagetic bone (p = 0.022), suggesting tighter binding of 18F-fluoride to bone mineral. The notional volume of the extravascular bone compartment (K1/k2) was greater in pagetic bone (p = 0.018). Although the unidirectional extraction efficiency from the extravascular space to bone mineral (Ki/K1) was greater in pagetic bone (p = 0.018), a lower pagetic value of k2 (p = 0.028), describing the rate of transfer from the bone extravascular compartment to plasma, suggests that the 18F-fluoride that enters the relatively fibrotic marrow space of pagetic bone may be less accessible for return to plasma. These findings confirm some of the known pathophysiology of Paget's disease, introduce some new observations, and show how dynamic 18F-fluoride PET may be of value in the measurement of regional metabolic parameters in focal bone disorders. 相似文献
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Detection of canine distemper virus in bone cells in the metaphyses of distemper-infected dogs. 总被引:1,自引:0,他引:1
A P Mee D M Webber C May D Bennett P T Sharpe D C Anderson 《Journal of bone and mineral research》1992,7(7):829-834
In the light of recent evidence implicating canine distemper virus (CDV) as a possible etiologic agent in Paget's disease of bone, we thought that it would be of interest to examine distemper-infected bone in the natural host. Samples from the long bones, spleen, and bladder of four distemper-infected and three uninfected dogs were examined for the presence of CDV nucleocapsid and phosphoprotein genes and the measles virus (MV) nucleocapsid gene using the technique of in situ hybridization with radioactively labeled riboprobes. Two of the four distemper-infected dogs showed strongly positive hybridization with both of the CDV probes. The signal was present in marrow cells, in osteoblasts, in osteocytes, and particularly in osteoclasts. No hybridization was seen over the cartilage cells of the growth plate, and there was a clear line of demarcation at the point of invasion of osteoclasts and vascularization. The spleen and bladder samples from infected dogs also showed positive hybridization. There was no hybridization with the MV probe in any of the distemper-infected tissue. Samples from the uninfected dogs showed no evidence of hybridization with either the CDV or MV probes. These results show that CDV can infect bone cells of the natural host and provide further support for the theory that CDV may play a role in human Paget's disease of bone. 相似文献
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Rendina D Mossetti G Soscia E Sirignano C Insabato L Viceconti R Ignarra R Salvatore M Nunziata V 《Clinical orthopaedics and related research》2004,(421):218-224
Giant cell tumor is a rare complication of Paget's disease of bone. Typically, this tumor occurs in the case of polyostotic disease and only in pagetic bones. This tumor rarely has been seen in multiple family members who have Paget's disease, although Paget's bone disease clearly has a hereditary component. Our report documents four cases of polyostotic Paget's bone disease complicated by benign giant cell tumor. In two patients, the giant cell tumor also was multifocal. All patients were from one family. They were born in Avellino and reside in Campania, a Southern Italian region. The ancestors of the patients with familial giant cell tumor in Paget's bone disease were born in the same geographic area. These data suggest that a combination of environmental and genetic factors could be responsible for linkage of the patients born in Avellino with this neoplasm that is highly unusual in patients with Paget's disease of bone. 相似文献
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On the trail of paramyxoviruses in Paget's disease of bone 总被引:3,自引:0,他引:3
M F Baslé A Rebel J G Fournier W C Russell K Malkani 《Clinical orthopaedics and related research》1987,(217):9-15
The ultrastructural discovery of microcylindric inclusions in the nuclei and cytoplasm of osteoclasts in tissue affected by Paget's disease of bone has created a new approach. The morphologic similarity of the inclusions to viral structures has stimulated further studies involving immunocytologic techniques and in situ hybridization. Polyclonal antibodies reveal the presence of paramyxovirus antigens and measles virus and respiratory syncytial virus in pagetic osteoclasts. Monoclonal and monospecific polyclonal antibodies demonstrate paramyxovirus antigens of measles virus, simian virus (SV5), and human parainfluenza virus (PF3). In situ hybridization carried out with a 3H-labeled DNA probe, specific for the measles nucleocapsid protein, detects measles virus nucleotide sequences in the nuclei and cytoplasm of pagetic osteoclasts, confirming ultrastructural and immunocytologic findings. Surprisingly, the tritiated probe also hybridizes with a large proportion of mononucleated cells: osteoblasts, osteocytes, fibroblasts, and lymphocytes. This suggests a very wide host cell range for measles virus genomic information which, however, would appear to undergo translation only in osteoclasts. The cause-effect relation between the viral information contained by diseased bone cells and Paget's disease of bone remains to be established. 相似文献
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This study evaluates previous viral antigen data obtained from fixed tissue sections and cells grown in culture from bone affected by Paget's disease. Finding antigens to both respiratory syncytial virus (RSV) and measles virus (MV) in the same osteoclasts of ten patients could not be explained on the basis of any previously known cross-reactivity. Therefore, possible causes for these observations were sought. Monoclonal antibodies to viral proteins of RSV and MV were used to label proteins. Polyclonal antibodies that were monospecific and were produced exclusively in nonhuman species were used to rule out nonspecific reaction with human proteins. Antivimentin antibody was used to test the possibility of cross-reactivity with a cytoskeletal protein, as a second antibody F(ab')2 conjugated to fluorescein was used to rule out nonspecific reactivity with Fc receptors. Electron microscopy was used to evaluate bone cell cultures derived from Paget's bone in comparison with Paget's osteoclasts. Results showed that the pattern of monoclonal viral antibody labeling followed different patterns in different patients. Nonspecific reactivity was ruled out by significant negative and positive controls. Cross-reactivity with vimentin could not account for the positive immunofluorescent results because of an entirely different pattern of fluorescence in the same samples of live and fixed cells after colchemid treatment. It was concluded that specific viral antigens are present in osteoclasts and in cells grown from Paget's bone and that the present data are compatible with the possibility that Paget's disease of bone is a slow virus infection. 相似文献
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M. Laroche B. Delpech J. Bernard A. Constantin B. Mazières 《Calcified tissue international》1999,65(3):188-191
Third-generation bisphosphonates are now currently used in the treatment of Paget's disease of bone. Dual X-ray absorptiometry
may make it possible to quantify the action of these bisphosphonates on bone mineral density (BMD) in pagetic and nonpagetic
bone. We used Lunar DPX, a total-body software program (automatic analysis and/or manual windows according to the site and
bilateral or unilateral pagetic involvement) to study BMD in 28 patients (18 men, 10 women, mean age 69.8 years) with Paget's
disease before and 6 months after infusions of 60 mg (alkaline phosphatase <350 IU) or 120 mg (ALP >350 IU) of pamidronate.
Before treatment, in the 28 patients, the BMD of trabecular pagetic bone was 25% higher than that of nonpagetic bone; in cortical
pagetic bone the BMD was 35% higher. After treatment, the BMD of trabecular pagetic bone increased by only 1.17%. the BMD
of cortical pagetic bone increased by 1.37% whereas nonpagetic cortical bone lost 0.84%, independently of the levels of parathyroid
hormone or the administration of calcium and vitamin D.
Received: 17 March 1998 / Accepted: 12 March 1999 相似文献
17.
Cells obtained from surgical bone specimens of eight patients with Paget's disease of bone were maintained in culture for up to 8 months and seven passages. The doubling time during the period of maximal cell growth ranged from 4 to 12 days. Evidence consistent with the hypothesis that many of the cells were bone cells included the following: (a) histochemical techniques demonstrated staining of some cells for alkaline phosphatase or acid phosphatase and succinic dehydrogenase; (b) parathyroid extract stimulated increased uptake of 3H-thymidine and 3H-uridine; (c) parathyroid extract suppressed and salmon calcitonin stimulated uptake of 3H-proline; and (d) crystalline calcium deposits were found within cells and extracellularly. Ultrastructural analysis revealed that three of the eight cultures contained cells whose nuclei had inclusions which were almost identical to those found in the osteoclast nuclei of all patients with Paget's disease. The maintenance of cells derived from pagetic bone in long-term culture should aid in testing the hypothesis that Paget's disease represents a slow virus infection of bone. 相似文献
18.
Malignant change in Paget's disease of bone usually has the histological features of osteosarcoma, but follows a different clinical course from cases not associated with paget's disease of bone. Malignant fibrous histiocytoma is an uncommon neoplasm which may be associated with pagetic bone and its clinical course is not well defined. Seven cases of malignant fibrous histiocytoma in Paget's disease were reviewed from two Australian bone tumour registries. In stage IIB and III disease there was a three year survival rate of 57%, suggesting a better prognosis than for patients with other sarcomas in Paget's disease. 相似文献
19.
Low back pain in Paget's disease of bone 总被引:1,自引:0,他引:1
Clinical and laboratory evaluation with bone scan, radiography, and computed tomography were performed on 25 patients with severe Paget's disease of bone and low back pain. Back pain was classified as caused by Paget's disease in only three patients. The remaining 22 patients had coexistent Paget's disease and osteoarthritis. There was difficulty separating the cause of back pain in those patients with coexistent Paget's disease and osteoarthritis, even when the diseases were present at different levels of the spine. The pathogenesis of Paget's disease appears to precipitate osteoarthritis and several low back syndromes. Suppressive therapy with disodium etidronate (EHDP) for Paget's disease was of benefit in eight of 22 patients (36%) with identifiable osteoarthritis. It is suggested that EHDP and perhaps other suppressive agents for Paget's disease receive limited use in patients with back pain unless a defined pagetic lesion appears related to the clinical syndrome in the absence of identifiable osteoarthritis. 相似文献
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Dr. Giulio Pioli M.D. Giuseppe Girasole Mario Pedrazzoni Paolo Sansoni Annalaura Erroi Luisa Davoli Giuseppina Ciotti Alberto Mantovani Mario Passeri 《Calcified tissue international》1989,45(4):257-259
Summary The Authors examined interleukin 1 (IL-1) secretion from the peripheral and medullary mononuclear cells, obtained with sequential
separation on Ficoll-Hypaque and 45% Percoll gradient, in 6 pagetic subjects and 6 normal controls. Both peripheral and medullary
cells from pagetic subjects showed a significantly greater IL-1 production after stimulation with lipopolyshaccarides (LPS);
moreover, we observed a spontaneous IL-1 release from medullary cells in pagetic subjects but not in normal controls. These
findings suggest a possible role of IL-1 in the elevated bone turnover of Paget's disease of bone. 相似文献