A role for bone morphogenetic protein-4 in adipocyte development
A role for bone morphogenetic protein-4 in adipocyte development
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DOI：
10.4161/cc.6.4.3804
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发表时间：
2007-02-15
期刊：
影响因子：
4.3
通讯作者：
Lane, M. Daniel
中科院分区：
文献类型：
--
作者：
Bowers, Robert R.;Lane, M. Daniel
肥胖症的特征是成熟脂肪细胞数量增加。新生脂肪细胞是由间充质干细胞（mesenchymal stem cells，MSCs）通过多步骤过程产生的--MSCs被募集到脂肪细胞谱系中形成确定的前脂肪细胞，这些定向祖细胞增殖，经历生长停滞，最终分化为成熟脂肪细胞。虽然控制前脂肪细胞分化为成熟脂肪细胞的遗传机制在很大程度上是了解的，在脂肪发生的最早期的事件，特别是骨髓间充质干细胞的承诺，成为前脂肪细胞在很大程度上是未知的。最近，骨形态发生蛋白-4（BMP-4）已被牵连的承诺，多能间充质干细胞的脂肪细胞谱系的两个独立的调查线。首先，生长停滞的10 T1/2细胞通常不响应于导致各种生长停滞的前脂肪细胞系分化成脂肪细胞的激素混合物，但是如果10 T1/2细胞首先用BMP-4处理，则它们将通过经历终末脂肪细胞分化来响应于这些激素诱导剂。第二，在将细胞暴露于DNA甲基转移酶抑制剂5-氮杂胞苷后，衍生自10 T1/2细胞的前脂肪细胞细胞系A33细胞显示表达BMP-4，并且这种内源性BMP-4表达是获得这些细胞的前脂肪细胞表型所需的。BMP-4信号通路在脂肪形成中的作用进行了讨论。
Obesity is characterized by increases in the number of mature adipocytes. Nascent adipocytes arise from mesenchymal stem cells (MSCs) by a multi-step process-MSCs are recruited to the adipocyte lineage forming determined preadipocytes, these committed progenitors proliferate, undergo growth arrest, and finally differentiate into mature adipocytes. Although the genetic mechanisms that control the differentiation of preadipocytes into mature adipocytes are understood to a large extent, the earliest events in adipogenesis-especially the commitment of MSCs into preadipocytes-are largely unknown. Recently, bone morphogenetic protein-4 (BMP-4) has been implicated in the commitment of pluripotent MSCs to the adipocyte lineage by two independent lines of investigation. First, growth-arrested 10T1/2 cells do not normally respond to a hormonal cocktail that causes various growth-arrested preadipocyte cell lines to differentiate into adipocytes, but if 10T1/2 cells are first treated with BMP-4 they will respond to these hormonal inducers by undergoing terminal adipocyte differentiation. Second, a preadipocyte cell line, A33 cells, derived from 10T1/2 cells after exposing the cells to the DNA methyltransferase inhibitor 5-azacytidine was shown to express BMP-4, and this endogenous BMP-4 expression is required for acquisition of the preadipocyte phenotype of these cells. A role for the BMP-4 signaling pathway in adipogenesis is discussed.