Osteoblast-specific expression of Fra-2/AP-1 controls adiponectin and osteocalcin expression and affects metabolism
Osteoblast-specific expression of Fra-2/AP-1 controls adiponectin and osteocalcin expression and affects metabolism
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DOI：
10.1242/jcs.134510
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发表时间：
2013-12-01
影响因子：
4
通讯作者：
Wagner, Erwin F.
中科院分区：
文献类型：
--
作者：
Bozec, Aline;Bakiri, Latifa;Wagner, Erwin F.
近年来的研究表明，骨骼作为一种内分泌器官，通过成骨细胞来源的激素骨钙素（osteocalcin, Ocn）影响代谢。然而，对于成骨细胞中表达的多少转录因子调控内分泌功能尚不完全清楚。在这里，我们发现Fra-2 （Fosl2）成骨特异性缺失的小鼠骨量低，但体重增加。相反，在成骨细胞中转基因表达fr -2可导致骨量增加、体重下降，同时降低血清葡萄糖和胰岛素水平，改善葡萄糖耐量和胰岛素敏感性。此外，缺乏fr -2的小鼠循环Ocn水平降低，但高脂联素（Adipoq）水平降低，而fr -2转基因小鼠表现出高Ocn和低Adipoq水平。此外，我们发现Adipoq在成骨细胞中表达，并且这种表达受到fr -2的转录抑制。这些结果表明，Fra-2在成骨细胞中的表达代表了一种控制骨骼内分泌功能的转录因子的新范式。
Recent studies have established that the skeleton functions as an endocrine organ affecting metabolism through the osteoblast-derived hormone osteocalcin (Ocn). However, it is not fully understood how many transcription factors expressed in osteoblasts regulate the endocrine function. Here, we show that mice with osteoblast-specific deletion of Fra-2 (Fosl2) have low bone mass but increased body weight. In contrast, transgenic expression of Fra-2 in osteoblasts leads to increased bone mass and decreased body weight accompanied by reduced serum glucose and insulin levels, improved glucose tolerance and insulin sensitivity. In addition, mice lacking Fra-2 have reduced levels of circulating Ocn, but high adiponectin (Adipoq), whereas Fra-2 transgenic mice exhibit high Ocn and low Adipoq levels. Moreover, we found that Adipoq was expressed in osteoblasts and that this expression was transcriptionally repressed by Fra-2. These results demonstrate that Fra-2 expression in osteoblasts represents a novel paradigm for a transcription factor controlling the endocrine function of the skeleton.