Overexpression of ΔFosB transcription factor(s) increases bone formation and inhibits adipogenesis
Overexpression of ΔFosB transcription factor(s) increases bone formation and inhibits adipogenesis
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DOI：
10.1038/79683
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发表时间：
2000-09-01
期刊：
影响因子：
82.9
通讯作者：
Baron, R
中科院分区：
文献类型：
--
作者：
Sabatakos, G;Sims, NA;Baron, R
转录因子AP-1家族的成员参与骨细胞增殖和分化的调节。我们在这里报告一个有效的AP-1相关的调节成骨细胞功能：三角洲FosB，一种天然存在的截短形式的FosB，从选择性剪接的FosB转录本，并在成骨细胞中表达。在转基因小鼠中过量表达Delta FosB导致整个骨骼的骨形成增加，以及骨量的持续发育后增加，从而导致骨质疏松。相反，Delta FosB在体内和体外均抑制脂肪形成，并下调脂肪细胞分化的早期标志物的表达。由于成骨细胞和脂肪细胞被认为是共享一个共同的前体，它的结论是，三角洲FosB转录调节成骨细胞的形成，可能是在脂肪形成的代价。
Members of the AP-1 family of transcription factors participate in the regulation of bone cell proliferation and differentiation. We report here a potent AP-1-related regulator of osteoblast function: Delta FosB, a naturally occurring truncated form of FosB that arises from alternative splicing of the fosB transcript and is expressed in osteoblasts. Overexpression of Delta FosB in transgenic mice leads to increased bone formation throughout the skeleton and a continuous post-developmental increase in bone mass, leading to osteosclerosis. In contrast, Delta FosB inhibits adipogenesis both in vivo and in vitro, and downregulates the expression of early markers of adipocyte differentiation. Because osteoblasts and adipocytes are thought to share a common precursor, it is concluded that Delta FosB transcriptionally regulates osteoblastogenesis, possibly at the expense of adipogenesis.