Ultrastructural features of the osteoclasts from Paget's disease of bone in relation to a viral aetiology.

Harvey, L.; Gray, Thomas; Benéton, M. N. C.; Douglas, D. L.; Kanis, John А.; Russell, R. G. G.

doi:10.1136/jcp.35.7.771

Cited by 58 publications

(31 citation statements)

References 29 publications

(4 reference statements)

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“…In 80 to 9 0~ of these multinucleated cells, hybridization reactions were observed both in the cytoplasm, with a diffuse distribution, and in some of the numerous nuclei, with different levels of intensity. Autoradiographic grains were sometimes concentrated and localized over the nuclear area, in particular over clear nuclear inclusions which very probably correspond to the nuclear accumulation of specific microcytinders as previously described in Pagetic osteoclasts (Gherardi et al, 1980;Harvey et al, 1982;Mills & Singer, 1976;Rebel et al, 1980bRebel et al, , 1974.…”

Section: Resultsmentioning

confidence: 87%

“…These findings are consistent with the ultrastructural and immunocytological observations previously described. Electron microscopical studies have shown that the cytoplasm and nuclei of osteoclasts from Paget's bone tissue contain microcylindrical inclusions very similar to measles virus nucleocapsids (Gherardi et al, 1980;Harvey et al, 1982;Howatson & Fornasier, 1982;Rebel et al, 1980b). Immunological experiments have also demonstrated the presence of measles nucleocapsid protein antigens both in cytoplasm and in nuclei of Pagetic osteoclasts (Basl6 et al, 1979(Basl6 et al, , 1985Rebel et al, 1980a).…”

Section: Discussionmentioning

confidence: 97%

“…Ultrastructural studies have shown the presence of specific inclusions in the enormous, multinucleated osteoclasts from Pagetic bone tissue. Morphological analyses have demonstrated that the structure, the dimensions and the cytoplasmic and nuclear distribution of the microcylindrical inclusions observed in Pagetic osteoclasts are very similar to the nucleocapsids found in cells infected with paramyxoviruses (Gherardi et al, 1980;Harvey et al, 1982;Howatson & Fornasier, 1982;Mills & Singer, 1976;Rebel et al, 1980bRebel et al, , 1974. Furthermore, using immunocytological techniques with polyclonal antibodies, several studies have demonstrated that osteoclasts from bone tissue in Paget's disease contain antigenic material related to measles virus and to respiratory syncytial virus, both of which are members of the family Paramyxoviridae (Basl6 et al, 1979;Mills et al, 1982;Rebel et al, 1980a;Singer & Mills, 1983).…”

Section: Introductionmentioning

confidence: 99%

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Measles Virus RNA Detected in Paget's Disease Bone Tissue by in situ Hybridization

Basle

Fournier

Rozenblatt

et al. 1986

Journal of General Virology

151

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SUMMARYMorphological and immunocytological studies have demonstrated the presence of paramyxovirus antigens in Paget's bone disease tissue and in particular antigens related to measles virus and respiratory syncytial virus. To examine the relationship between measles virus and Paget's bone disease we used in situ hybridization and a cloned measles virus DNA probe specific for the nucleocapsid protein to detect and locate measles virus RNA sequences in Paget's bone tissue. In five patients with the disease, measles virus RNA sequences were detected not only in 80 to 90% of the multinucleated osteoclasts where there is morphological and immunocytological evidence of measles virus activity but also in 30 to 40% of mononucleated bone cells, mainly osteoblasts, osteocytes, fibroblasts and lympho-monocytes. In contrast, no hybridization was observed in bone tissue from three control patients without signs of Paget's bone disease. These results indicate that the host cell range for measles virus in Paget's disease is more widespread than has been supposed. They also demonstrate the usefulness of the in situ hybridization method to detect viral genetic information in cells where viral antigenic activity is not detectable. These observations further support the hypothesis that measles virus is involved in the pathogenesis of Paget's bone disease.

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Section: Resultsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Measles Virus RNA Detected in Paget's Disease Bone Tissue by in situ Hybridization

Basle

Fournier

Rozenblatt

et al. 1986

Journal of General Virology

151

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“…Italy, (4) Canada, (5) the United Kingdom, (6,7) Japan, (8)(9)(10) and Czechoslovakia. (11) Osteoclasts in subjects with normal bone did not exhibit the abnormality.…”

Section: Osteoclastsmentioning

confidence: 99%

Ultrastructure of Bone Cells in Paget's Disease of Bone

Singer

Mills

Gruber

et al. 2006

Journal of Bone and Mineral Research

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“…All other authors state that they have no conflicts of interest. 1 University of Pittsburgh, Department of Medicine/Hematology-Oncology, Pittsburgh, Pennsylvania, USA; normal OCLs. Furthermore, both pagetic and MVNPtransfected normal OCL precursors display marked hyperresponsivity to 1,25(OH) 2 D 3 , forming OCLs at concentrations that are 1-2 logs lower than required for normal OCL formation.…”

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confidence: 99%

Experimental Models of Paget's Disease

Kurihara

Zhou

Reddy³

et al. 2006

Journal of Bone and Mineral Research

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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) is one of the most exaggerated examples of abnormal bone remodeling, with increased bone resorption and excessive new bone formation. However, its etiology is unclear. A viral etiology for PD has been suggested based on the presence of paramyxoviral-like nuclear inclusions, detection of measles virus nucleocapsid (MVNP) mRNA or protein in osteoclasts (OCLs) from PD lesions, and in vitro studies showing that transfection of normal OCL precursors with the MVNP gene results in formation of OCLs that express a pagetic phenotype (increased numbers of OCLs; increased responsivity to 1,25(OH) 2 D 3 , RANKL, and TNF-␣; increased expression of the TAF II -17 gene, and increased bone resorption capacity). Materials and Methods:We targeted MVNP to cells in the OCL lineage in transgenic mice using the TRACP promoter. Results: Histomorphometric analysis showed that there was a 64% increase in OCL perimeter (p ‫ס‬ 6.0002) and 37% increase in osteoblast (OBL) perimeter in MVNP mice. In a mouse that was 14 months of age, there was a 225% increase in OBL perimeter and 149% in OBL perimeter. This was accompanied by increased cancellous bone volume (83%) and trabecular width (47%) and number (25%), with a marked increase in the amount of woven bone. In contrast, cancellous bone volume decreased between 3 and 12 months in wildtype (WT) mice, whereas cancellous bone volume in MVNP mice increased over the same time period. Ex vivo studies showed that the numbers of OCLs formed in marrow cultures from MVNP mice were increased, and the OCLs were hyper-responsive to 1,25(OH) 2 D 3 and had an increased bone resorbing capacity compared with WT cultures. Conclusion: These results show that expression of MVNP in OCL in vivo results in a bone phenotype that is characteristic of PD.

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Ultrastructural features of the osteoclasts from Paget's disease of bone in relation to a viral aetiology.

Cited by 58 publications

References 29 publications

Measles Virus RNA Detected in Paget's Disease Bone Tissue by in situ Hybridization

Measles Virus RNA Detected in Paget's Disease Bone Tissue by in situ Hybridization

Ultrastructure of Bone Cells in Paget's Disease of Bone

Experimental Models of Paget's Disease

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