Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice

Noriyoshi Kurihara, Hua Zhou, Sakamuri V. Reddy, Veronica Garcia Palacios, Mark A. Subler, David W. Dempster, Jolene J. Windle, G. David Roodman

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)446-455
Number of pages10
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume21
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Fingerprint

Osteitis Deformans
Measles virus
Osteoclasts
Nucleocapsid
Bone and Bones
Transgenic Mice
Genes
measles virus nucleocapsid protein
Virus Receptors
Bone Diseases
Cell Lineage
Virus Diseases
Bone Marrow Cells
Transfection
Interleukin-6

Keywords

  • IL-6
  • Measles virus nucleocapsid
  • Osteoclast
  • Paget's disease
  • TAF-17

ASJC Scopus subject areas

  • Surgery

Cite this

Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice. / Kurihara, Noriyoshi; Zhou, Hua; Reddy, Sakamuri V.; Palacios, Veronica Garcia; Subler, Mark A.; Dempster, David W.; Windle, Jolene J.; Roodman, G. David.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 21, No. 3, 03.2006, p. 446-455.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Zhou, Hua

AU - Reddy, Sakamuri V.

AU - Palacios, Veronica Garcia

AU - Subler, Mark A.

AU - Dempster, David W.

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AU - Roodman, G. David

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