Ebf1-dependent control of the osteoblast and adipocyte lineages.
Ebf1-dependent control of the osteoblast and adipocyte lineages.
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DOI：
10.1016/j.bone.2008.11.021
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发表时间：
2009-04
期刊：
影响因子：
4.1
通讯作者：
Horowitz, Mark C.
中科院分区：
文献类型：
--
作者：
Hesslein, David G. T.;Fretz, Jackie A.;Xi, Yougen;Nelson, Tracy;Zhou, Shoaming;Lorenzo, Joseph A.;Schatz, David G.;Horowitz, Mark C.
Ebf1 是 B 细胞命运规范和功能所必需的转录因子，对嗅觉感觉神经元的发育也很重要。我们在此表明，Ebf1 在调节体内成骨细胞和脂肪细胞发育中也发挥着重要作用。 Ebf1 mRNA 和蛋白质在 MSC、大多数分化阶段的 OB 以及脂肪细胞中表达。 Ebf1−/− 小鼠的胫骨和股骨的所有骨形成参数均显着增加，包括 OB 数量、类骨质体积和骨形成率。血清骨钙素（骨形成的标志物）在突变小鼠中显着升高。骨中破骨细胞的数量在年轻（4周龄）Ebf1−/−小鼠中是正常的，但在年老（12周龄）Ebf1−/−小鼠中增加。这与体外骨髓细胞的破骨细胞发育密切相关。除了成骨细胞生成增加之外，Ebf1−/− 小鼠骨髓中的脂肪细胞数量也显着增加。组织学上还发现这些小鼠的肝脏中脂肪含量增加，但脾脏中没有，并且伴随着皮下部位脂肪沉积的减少。因此，Ebf1 缺陷小鼠似乎是一种新的脂肪营养不良模型。 Ebf1 是转录因子的一个罕见例子，它可以类似地调节成骨细胞和脂肪细胞谱系。
Ebf1 is a transcription factor essential for B cell fate specification and function and important for the development of olfactory sensory neurons. We show here that Ebf1 also plays an important role in regulating osteoblast and adipocyte development in vivo. Ebf1 mRNA and protein is expressed in MSCs, in OBs at most stages of differentiation, and in adipocytes. Tibiae and femora from Ebf1−/− mice had a striking increase in all bone formation parameters examined including the number of OBs, osteoid volume, and bone formation rate. Serum osteocalcin, a marker of bone formation, was significantly elevated in mutant mice. The numbers of osteoclasts in bone were normal in younger (4 week-old) Ebf1−/− mice but increased in older (12 week-old) Ebf1−/− mice. This correlated well with in vitro osteoclast development from bone marrow cells. In addition to the increased osteoblastogenesis, there was a dramatic increase in adipocyte numbers in the bone marrow of Ebf1−/− mice. Increased adiposity was also seen histologically in the liver but not in the spleen of these mice, and accompanied by decreased deposition of adipose to subcutaneous sites. Thus Ebf1-deficient mice appear to be a new model of lipodystrophy. Ebf1 is a rare example of a transcription factor that regulates both the osteoblast and adipocyte lineages similarly.
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