acid-phosphatase and Measles

Pagetic osteoclasts (OCLs) are abnormal in size and contain paramyxoviral-like nuclear inclusions that cross-react with antibodies to measles virus (MV). 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 targeted a cellular MV receptor, human CD46 (hCD46), to cells in the OCL lineage in transgenic mice using the mouse tartrate-resistant acid phosphatase (TRAP) gene promoter. In vitro infection of OCL precursors from hCD46 transgenic mice with MV significantly increased OCL formation in bone marrow cultures. The numbers of TRAP-positive mononuclear cells and CFU-GM, the earliest identifiable OCL precursor, were also significantly increased. MV-infected OCLs formed from hCD46 marrow were increased in size, contained markedly increased numbers of nuclei, and had increased bone-resorbing capacity per OCL compared with OCLs formed from marrow of nontransgenic littermates. Furthermore, IL-6 and 24-hydroxylase messenger RNA expression levels were increased in MV-infected hCD46 transgenic mouse bone marrow cultures. Treatment of MV-infected hCD46 marrow cultures with a neutralizing antibody to IL-6 blocked the increased OCL formation seen in these cultures. These data demonstrate that MV infection of OCL precursors results in OCLs that have many features of pagetic OCLs, that the enhanced OCL formation is in part mediated 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.

Topics: Acid Phosphatase; Animals; Antigens, CD; Bone Marrow Cells; Bone Resorption; Cell Division; Humans; Interleukin-6; Isoenzymes; Measles; Membrane Cofactor Protein; Membrane Glycoproteins; Mice; Mice, Transgenic; Osteitis Deformans; Osteoclasts; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stem Cells; Tartrate-Resistant Acid Phosphatase

The detection of virus in osteoclasts from Pagetic patients is now well known, but it has yet to be shown convincingly that the presence of virus in Pagetic osteoclasts influences their behaviour. In this study, osteoclasts from embryonic chick tibiae were infected with canine distemper virus or measles virus and compared with mock-infected controls. Infection was confirmed using virus-specific fluorescent antibodies. It was found that virus infection did not alter osteoclast morphology or tartrate-resistant acid phosphatase (TRAP) activity. Both infected and mock-infected osteoclasts produced resorption pits on bovine bone slices; these could be divided into two distinct size classes with a computer-based measuring system. Virus infection significantly increased the proportion of the larger size class of resorption pit. These results suggest that virus infection can increase bone resorption by osteoclasts, lending further support to the hypothesis that viruses play a role in Paget's disease of bone.

Topics: Acid Phosphatase; Animals; Bone Resorption; Cell Culture Techniques; Chick Embryo; Distemper; Distemper Virus, Canine; Fluorescent Antibody Technique; Isoenzymes; Measles; Osteitis Deformans; Osteoclasts; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Adenovirus Infections, Human; Arachis; Carboxylic Ester Hydrolases; Chickenpox; Cytomegalovirus Infections; Humans; Influenza, Human; Measles; Paramyxoviridae Infections; Pneumonia, Viral; Receptors, Mitogen; Respiratory Syncytial Viruses; Respirovirus Infections