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Transgenic Mice Overexpressing Macrophage Migration Inhibitory Factor (MIF) Exhibit High‐Turnover Osteoporosis
Author(s) -
Onodera Shin,
Sasaki Satoshi,
Ohshima Shigeki,
Amizuka Norio,
Li Minqi,
Udagawa Nobuyuki,
Irie Kazuharu,
Nishihira Jun,
Koyama Yoshikazu,
Shiraishi Ayako,
Tohyama Harukazu,
Yasuda Kazunori
Publication year - 2006
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.060310
Subject(s) - bone remodeling , endocrinology , medicine , bone resorption , macrophage migration inhibitory factor , cathepsin k , osteoclast , genetically modified mouse , bone marrow , osteoporosis , chemistry , transgene , biology , receptor , cytokine , biochemistry , gene
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, μCT, 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: μCT 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.