Interferon-γ Plays a Role in Bone Formation In Vivo and Rescues Osteoporosis in Ovariectomized Mice
Interferon-γ Plays a Role in Bone Formation In Vivo and Rescues Osteoporosis in Ovariectomized Mice
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DOI：
10.1002/jbmr.350
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发表时间：
2011-07-01
影响因子：
6.2
通讯作者：
Kremer, Richard
中科院分区：
文献类型：
--
作者：
Duque, Gustavo;Huang, Dao Chao;Kremer, Richard
干扰素γ（IFN-γ）是一种由免疫源细胞和间充质干细胞在骨微环境中局部产生的细胞因子。然而，它在正常骨重塑中的作用仍然知之甚少。在本研究中，我们首先在表达 IFN-gamma 受体敲除表型 (IFN-gamma R1(-/-)) 的 C57BL/6 小鼠体内检查 IFN-gamma 消融的后果。与野生型同窝小鼠（IFN γ R1（+/+））相比，IFN γ R1（-/-）小鼠表现出骨体积减少，与骨质疏松表型特征的皮质和小梁结构参数的显着变化相关。 IFNγR1(-/-)小鼠的骨组织形态计量显示出低骨转换模式，骨形成减少，成骨细胞和破骨细胞数量显着减少，骨形成和骨吸收标志物的循环水平降低。此外，对野生型 C57BL/6 假手术 (SHAM) 和卵巢切除 (OVX) 雌性小鼠施用 IFN-γ（2000 和 10,000 单位）可显着改善 SHAM 小鼠的骨量和微结构、骨的机械性能以及骨形成与骨吸收之间的比率，并挽救 OVX 小鼠的骨质疏松症。因此，这些数据支持 IFN-γ 信号传导作为骨质疏松症潜在新合成代谢治疗靶点的重要生理作用。 (C) 2011 年美国骨与矿物质研究学会。
Interferon gamma (IFN-gamma) is a cytokine produced locally in the bone microenvironment by cells of immune origin as well as mesenchymal stem cells. However, its role in normal bone remodeling is still poorly understood. In this study we first examined the consequences of IFN-gamma ablation in vivo in C57BL/6 mice expressing the IFN-gamma receptor knockout phenotype (IFN gamma R1(-/-)). Compared with their wild-type littermates (IFN gamma R1(+/+)), IFN gamma R1(-/-) mice exhibit a reduction in bone volume associated with significant changes in cortical and trabecular structural parameters characteristic of an osteoporotic phenotype. Bone histomorphometry of IFN gamma R1(-/-) mice showed a low-bone-turnover pattern with a decrease in bone formation, a significant reduction in osteoblast and osteoclast numbers, and a reduction in circulating levels of bone-formation and bone-resorption markers. Furthermore, administration of IFN-gamma (2000 and 10,000 units) to wildtype C57BL/6 sham-operated (SHAM) and ovariectomized (OVX) female mice significantly improved bone mass and microarchitecture, mechanical properties of bone, and the ratio between bone formation and bone resorption in SHAM mice and rescued osteoporosis in OVX mice. These data therefore support an important physiologic role for IFN-gamma signaling as a potential new anabolic therapeutic target for osteoporosis. (C) 2011 American Society for Bone and Mineral Research.