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


BACKGROUND
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.


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.
Kurihara
Noriyoshi
N
Medicine/Hem-Onc, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Zhou
Hua
H
Reddy
Sakamuri V
SV
Garcia Palacios
Veronica
V
Subler
Mark A
MA
Dempster
David W
DW
Windle
Jolene J
JJ
Roodman
G David
GD
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D015870:Gene Expression; D005814:Genes, Viral; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008459:Measles virus / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D019590:Nucleocapsid Proteins / Q000235:genetics*; D010001:Osteitis Deformans / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D010010:Osteoclasts / Q000378:metabolism / Q000821:virology*
D015850:Interleukin-6; D019590:Nucleocapsid Proteins