Osteoclasts expressing the measles virus nucleocapsid gene display a pagetic phenotype

Osteoclasts (OCLs) in Paget's disease are markedly increased in number and size, have increased numbers of nuclei per multinucleated cell, and demonst rate increased resorption capacity and increased sensitivity to 1,25-(OH)(2 )D-3, the active form of vitamin D. These cells also contain nuclear inclus ions, reminiscent of those seen in paramyxovirus-infected cells, which cros s-react with antibodies to measles virus nucleocapsid (MVNP) antigen. To el ucidate the role of MV in the abnormal OCL phenotype of Paget's disease, we transduced normal OCL precursors with retroviral vectors expressing MVNP a nd the MV matrix (MVM) genes. The transduced cells were then cultured with 1,25-(OH)(2)D-3 for 14 or 21 days to induce formation of OCL-like multinucl eated cells. The MVNP-transduced cells formed increased numbers of multinuc leated cells, which contained many more nuclei and had increased resorption capacity compared with multinucleated cells derived from empty vector-tran sduced (EV-transduced) and MVM-transduced or normal bone marrow cells. Furt hermore, MVNP-transduced cells showed increased sensitivity to 1,25-(OH)(2) D-3, and formed OCLs at concentrations of 1,25-(OH)(2)D-3 that were 1 log l ower than that required for normal, EV-transduced, or MVM-transduced cells. These results demonstrate that expression of the MVNP gene in normal OCL p recursors stimulates OCL formation and induces OCLs that express a phenotyp e similar to that of pagetic OCLs. These results support a potential pathop hysiologic role for MV infection in the abnormal OCL activity and morpholog y that are characteristic of pagetic OCLs.