Overexpression of the granulocyte colony-stimulating factor gene leads to osteoporosis in mice.
Overexpression of the granulocyte colony-stimulating factor gene leads to osteoporosis in mice.
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粒细胞集落刺激因子基因的过度表达会导致小鼠骨质疏松症。
DOI：
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
S. Ishii
中科院分区：
文献类型：
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作者：
T. Takahashi;T. Wada;M. Mori;Y. Kokai;S. Ishii
虽然粒细胞集落刺激因子（G-CSF）最初是作为粒细胞谱系中细胞的生长和分化的活性而分离的，但已经逐渐接受G-CSF可能对除粒细胞之外的多种细胞具有功能。为了阐明G-CSF在体内对骨细胞的功能，我们检查了过表达G-CSF的转基因小鼠的骨组织。转基因小鼠在SR α启动子的指导下以升高的水平（血清中1041 +/-242 pg/ml）表达人G-CSF。我们进行了放射学，常规组织学，骨组织和血清生化测定的组织形态学分析。在所有实验中，将非转基因同窝仔作为年龄匹配的野生型对照进行检查。影像学分析显示椎体和长骨皮质变薄，伴有骨髓腔扩大。组织学上，在腰椎和股骨标本中观察到骨小梁数量和厚度减少以及皮质变薄。扩大的骨髓腔表现出成熟的嗜中性粒细胞数量增加，而其他类型的细胞无明显变化。反映骨吸收的静态和动态参数在转基因小鼠中被发现显着增加。相比之下，在反映骨形成的参数中没有检测到显著差异。转基因小鼠和同窝对照组具有相似的血清钙、磷和碱性磷酸酶水平。然而，血清骨钙素水平显着较高的转基因小鼠。这些发现表明，G-CSF表达转基因小鼠骨质疏松症的发展，因为增加骨代谢活性。总的来说，G-CSF可能对体内骨稳态产生负面影响。
Although granulocyte colony-stimulating factor (G-CSF) was originally isolated as an activity for the growth and differentiation of cells in granulocytic lineage, it has been gradually accepted that G-CSF may have a function on a wide variety of cells besides granulocytes. To elucidate the function of G-CSF on bone cells in vivo, we examined the bone tissue of transgenic mice that overexpress G-CSF. Transgenic mice express human G-CSF at an elevated level (1041 +/- 242 pg/ml in sera) under the direction of SRalpha promoter. We performed radiographic, routine histologic, and histomorphometric analyses of the bone tissue and serum biochemical assay. Nontransgenic littermates were examined as age-matched, wild-type controls in all experiments. Radiographic analysis revealed cortical thinning accompanied by enlarged bone marrow cavities in both vertebral bodies and long bones. Histologically, a decreased number and thickness of trabecular bones and cortical thinning were observed in lumber vertebrae as well as in femur specimens. The enlarged bone marrow cavities exhibited an increased number of mature neutrophilic granulocytes without apparent changes in other types of cells. The static and dynamic parameters reflecting bone resorption were found to be significantly increased in the transgenic mice. By contrast, no significant differences were detected in the parameters reflecting bone formation. Transgenic mice and littermate controls had similar serum calcium, phosphorous, and alkaline phosphatase levels. However, the serum osteocalcin level was significantly higher in transgenic mice. These findings indicate that G-CSF-expressing transgenic mice developed osteoporosis because of increased osteoclastic activity. Collectively, G-CSF could have a negative influence on bone homeostasis in vivo.