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

Reddy, S V; Kurihara, N; Menaa, C; Landucci, G; Forthal, D; Koop, B A; Windle, J J; Roodman, G D

Reddy, S V; Kurihara, N; Menaa, C; Landucci, G; Forthal, D; Koop, B A; Windle, J J; Roodman, G D.

Afiliación

Reddy SV; Department of Medicine/Hematology, University of Texas Health Science Center, San Antonio, Texas 78229, USA.

Endocrinology ; 142(7): 2898-905, 2001 Jul.

Article en En | MEDLINE | ID: mdl-11416009

RESUMEN

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.

Asunto(s)

Antígenos CD/metabolismo; Sarampión/patología; Glicoproteínas de Membrana/metabolismo; Osteítis Deformante/patología; Osteoclastos/patología; Células Madre/patología; Fosfatasa Ácida/genética; Fosfatasa Ácida/metabolismo; Animales; Antígenos CD/genética; Células de la Médula Ósea/metabolismo; Células de la Médula Ósea/patología; Resorción Ósea/fisiopatología; División Celular; Humanos; Interleucina-6/metabolismo; Isoenzimas/genética; Isoenzimas/metabolismo; Proteína Cofactora de Membrana; Glicoproteínas de Membrana/genética; Ratones; Ratones Transgénicos/genética; Osteítis Deformante/fisiopatología; Osteoclastos/fisiología; Fenotipo; ARN Mensajero/genética; ARN Mensajero/metabolismo; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa; Fosfatasa Ácida Tartratorresistente

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteítis Deformante / Osteoclastos / Células Madre / Glicoproteínas de Membrana / Antígenos CD / Sarampión Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Endocrinology Año: 2001 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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