Transgenic mice overexpressing macrophage migration inhibitory factor (MIF) exhibit high-turnover osteoporosis.

Onodera, Shin; Sasaki, Satoshi; Ohshima, Shigeki; Amizuka, Norio; Li, Minqi; Udagawa, Nobuyuki; Irie, Kazuharu; Nishihira, Jun; Koyama, Yoshikazu; Shiraishi, Ayako; Tohyama, Harukazu; Yasuda, Kazunori

Onodera, Shin; Sasaki, Satoshi; Ohshima, Shigeki; Amizuka, Norio; Li, Minqi; Udagawa, Nobuyuki; Irie, Kazuharu; Nishihira, Jun; Koyama, Yoshikazu; Shiraishi, Ayako; Tohyama, Harukazu; Yasuda, Kazunori.

Afiliación

Onodera S; Department of Sports Medicine and Joint Recontruction Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan. onodera@med.hokuda.ac.jp

J Bone Miner Res ; 21(6): 876-85, 2006 Jun.

Article en En | MEDLINE | ID: mdl-16753018

RESUMEN

UNLABELLED: The bone phenotype of mice overexpressing MIF was studied. These mice showed decreased trabecular bone, increased bone formation rate, and increased MMP-3, -9, and -13 mRNA expression in the femora and tibias. This model provides evidence of the role played by MIF in bone remodeling and balance in vivo. INTRODUCTION: The role of macrophage migration inhibitory factor (MIF) in in vivo bone remodeling remains unelucidated. We describe disordered bone metabolism in transgenic mice overexpressing MIF. MATERIALS AND METHODS: For in vivo study, muCT, bone histomorphometry, blood and urine biochemical data, and gene expression of MIF transgenic (MIF Tg) mice and littermate wildtype (WT) mice were examined. For in vitro study, osteoclastogenesis in the co-culture of bone marrow cells and osteoblasts from MIF Tg and WT were assessed. RESULTS: muCT analyses revealed a significant reduction in the trabecular bone of distal femur in MIF Tg at 8-12 weeks of age. Histomorphometric analysis revealed increase in several measures of bone formation. Osteoclastogenesis was not influenced by the origin of bone marrow cells or osteoblasts. Urine level of deoxypyridinoline/creatinine and the mRNA levels of matrix metalloproteinase (MMP) -3, -9, and -13 in femurs were elevated in MIF Tg. CONCLUSIONS: Overexpression of MIF causes high-turnover osteoporosis in mice. The increased expression of MMPs in bone was suggested, at least in part, as one cause of this phenotype, because MMPs plays important roles for bone resorption without affecting the formation of osteoclasts. This model provides evidence of the role played by MIF in bone remodeling and balance.

Asunto(s)

Factores Inhibidores de la Migración de Macrófagos/metabolismo; Macrófagos/metabolismo; Osteoporosis/genética; Osteoporosis/metabolismo; Aminoácidos/sangre; Aminoácidos/orina; Animales; Secuencia de Bases; Remodelación Ósea/genética; Proteínas Portadoras/metabolismo; Células Cultivadas; Creatinina/sangre; Creatinina/orina; Modelos Animales de Enfermedad; Fémur/patología; Factores Inhibidores de la Migración de Macrófagos/genética; Masculino; Glicoproteínas de Membrana/metabolismo; Ratones; Ratones Endogámicos C57BL; Ratones Transgénicos; Datos de Secuencia Molecular; Osteoblastos/metabolismo; Osteocalcina/sangre; Osteocalcina/orina; Osteoporosis/patología; Ligando RANK; ARN/biosíntesis; Receptor Activador del Factor Nuclear kappa-B; Regulación hacia Arriba

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoporosis / Factores Inhibidores de la Migración de Macrófagos / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Bone Miner Res Asunto de la revista: METABOLISMO / ORTOPEDIA Año: 2006 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos

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