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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Cbfb2 Isoform Dominates More Potent Cbfb1 and Is Required for Skeletal Development
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Cbfb2 Isoform Dominates More Potent Cbfb1 and Is Required for Skeletal Development

机译：CBFB2同种型占主导地位更有效的CBFB1，并且是骨骼发育所必需的

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Cbfb is a cotranscription factor that forms a heterodimer with Runx proteins Runx1, Runx2, and Runx3. It is required for fetal liver hematopoiesis and skeletal development. Cbfb has two functional isoforms, Cbfb1 and Cbfb2, which are formed by alternative splicing. To address the biological functions of these isoforms in skeletal development, we examined Cbfb1(-/-) and Cbfb2(-/-) mouse embryos. Intramembranous and endochondral ossification was retarded and chondrocyte and osteoblast differentiation was inhibited in Cbfb2(-/-) embryos but not in Cbfb1(-/-) embryos. Cbfb2 mRNA was upregulated in calvariae, limbs, livers, thymuses, and hearts of Cbfb1(-/-) embryos but Cbfb1 mRNA was not in those of Cbfb2(-/-) embryos, and the total amount of Cbfb1 and Cbfb2 mRNA in Cbfb1(-/-) embryos was similar to that in wild- type embryos but was severely reduced in Cbfb2(-/-) embryos. The absolute numbers of Cbfb2 mRNA in calvariae, limbs, livers, thymuses, and brains in wild- type embryos were about three times higher than those of Cbfb1 in the respective tissue. The levels of Runx proteins were reduced in calvariae, limbs, and primary osteoblasts from Cbfb2(-/-) embryos, but the reduction in Runx2 protein was very mild. Furthermore, the amounts of Runx proteins and Cbfb in Cbfb2(-/-) embryos differed similarly among skeletal tissues, livers, and thymuses, suggesting that Runx proteins and Cbfb are mutually required for their stability. Although Cbfb1(-/-) embryos developed normally, Cbfb1 induced chondrocyte and osteoblast differentiation and enhanced DNA binding of Runx2 more efficiently than Cbfb2. Our results indicate that modulations in the relative levels of the isoforms may adjust transcriptional activation by Runx2 to appropriate physiological levels. Cbfb2 was more abundant, but Cbfb1 was more potent for enhancing Runx2 activity. Although only Cbfb2 loss generated overt skeletal phenotypes, both may play major roles in skeletal development with functional redundancy. (C) 2016 American Society for Bone and Mineral Research.
机译：CBFB是一种与Runx蛋白Runx1，Runx2和Runx3形成异二聚体的基调因子。胎儿肝血液和骨骼发育是必需的。 CBFB具有两种功能性同种型，CBFB1和CBFB2，其通过替代剪接形成。为了解决这些同种型在骨骼发育中的生物学功能，我们检查了CBFB1（ - / - ）和CBFB2（ - / - ）小鼠胚胎。在CBFB 2（ - / - ）胚胎中抑制了肠腔静脉瘤和中肠球骨化，并且在CBFB 2（ - / - ）胚胎中抑制了软骨细胞和成骨细胞分化，但不抑制CBFB1（ - / - ）胚胎。 CBFB2 mRNA在CBFB1（ - / - ）胚胎的CALVARIAE，四肢，肝脏，胸腺和心脏中，但CBFB1 mRNA不在CBFB2（ - / - ）胚胎中，以及CBFB1中的CBFB1和CBFB2 mRNA的总量（ - / - ）胚胎类似于野生型胚胎中的胚胎，但在CBFB2（ - / - ）胚胎中严重降低。 CALVARIAE，四肢，肝脏，胸腺和野生型胚胎中的CBFB2 mRNA的绝对数量比各组织中的CBFB1高出三倍。 CBFB2（ - / - ）胚胎的Calvariae，四肢和初级成骨细胞中的Runx蛋白水平降低，但Runx2蛋白的还原非常温和。此外，CBFB2（ - / - ）胚胎中Runx蛋白和CBFB的量在骨骼组织，肝脏和胸腺中同样不同，表明Runx蛋白和CBFB相互需要它们的稳定性。虽然CBFB1（ - / - ）胚胎通常开发，但CBFB1诱导软骨细胞和成骨细胞分化，并比CBFB 2更有效地增强RUNX2的DNA结合。我们的结果表明，同种型的相对水平的调节可以通过RUNX2调整转录激活到适当的生理水平。 CBFB2更丰富，但CBFB1更有效地增强RUNX2活性。虽然只有CBFB2损失产生明显的骨骼表型，但两者都可能在骨骼发育中发挥主要作用，具有功能冗余。 （c）2016年美国骨骼和矿物学学会。

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