Osteoclasts formed by measles virus-infected osteoclast precursors from hCD46 transgenic mice express characteristics of pagetic osteoclasts

Pagetic osteoclasts (OCLs) are abnormal in size and contain paramyxoviral-l ike nuclear inclusions that cross-react with antibodies to measles virus (M V). However, the role that MV infection plays in Paget's disease is unknown , because no animal model of Paget's disease is available. Therefore, we ta rgeted a cellular MV receptor, human CD46 (hCD46), to cells in the OCL line age in transgenic mice using the mouse tartrate-resistant acid phosphatase (TRAP) gene promoter. In vitro infection of OCL precursors from hCD46 trans genic mice with MV significantly increased OCL formation in bone marrow cul tures. The numbers of TRAP-positive mononuclear cells and CFU GM, the earli est identifiable OCL precursor, were also significantly increased. MV-infec ted OCLs formed from hCD46 marrow were increased in size, contained markedl y increased numbers of nuclei, and had increased bone-resorbing capacity pe r OCL compared with OCLs formed from marrow of nontransgenic littermates. F urthermore, IL-6 and 24-hydroxylase messenger RNA expression levels were in creased in MV-infected hCD46 transgenic mouse bone marrow cultures. Treatme nt of MV-infected hCD46 marrow cultures with a neutralizing antibody to IL- 6 blocked the increased OCL formation seen in these cultures. These data de monstrate that MV infection of OCL precursors results in OCLs that have man y features of pagetic OCLs, that the enhanced OCL formation is in part medi ated by increased IL-6 expression induced by MV infection, and suggest that the hCD46 transgenic mouse may be a useful model for examining the effects of MV infection on OCL formation in vivo.