Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes.
Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes.
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DOI：
10.1083/jcb.153.1.87
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发表时间：
2001-04-02
期刊：
影响因子：
--
通讯作者：
Komori T
中科院分区：
文献类型：
--
作者：
Ueta C;Iwamoto M;Kanatani N;Yoshida C;Liu Y;Enomoto-Iwamoto M;Ohmori T;Enomoto H;Nakata K;Takada K;Kurisu K;Komori T
在骨骼形成过程中，软骨要么发育为终身存在的永久软骨，要么发育为最终被骨骼取代的短暂软骨。然而，软骨表型被指定的机制仍然不清楚。核心结合因子α1 （Cbfa1）是成骨细胞分化和骨形成的重要转录因子，在体外具有促进软骨细胞成熟的能力。为了了解Cbfa1在骨骼发育过程中在软骨细胞中的作用，我们在II型胶原启动子/增强子的控制下，在软骨细胞中过度表达Cbfa1或显性阴性(DN)-Cbfa1的转基因小鼠。两种类型的转基因小鼠都表现出侏儒症和骨骼畸形，然而，这是由相反的细胞表型引起的。Cbfa1过表达导致软骨细胞早熟成熟加速软骨内成骨，而DN-Cbfa1过表达抑制成熟并延迟软骨内成骨。此外，Cbfa1转基因小鼠的大部分关节和永久软骨进入软骨内通路，而DN-Cbfa1转基因小鼠的大部分软骨细胞保留了永久软骨的标记物。这些数据表明，在时间和空间上调节软骨细胞中Cbfa1的表达是骨骼形成所必需的，包括关节、永久软骨和软骨内骨的形成。
During skeletogenesis, cartilage develops to either permanent cartilage that persists through life or transient cartilage that is eventually replaced by bone. However, the mechanism by which cartilage phenotype is specified remains unclarified. Core binding factor α1 (Cbfa1) is an essential transcription factor for osteoblast differentiation and bone formation and has the ability to stimulate chondrocyte maturation in vitro. To understand the roles of Cbfa1 in chondrocytes during skeletal development, we generated transgenic mice that overexpress Cbfa1 or a dominant negative (DN)-Cbfa1 in chondrocytes under the control of a type II collagen promoter/enhancer. Both types of transgenic mice displayed dwarfism and skeletal malformations, which, however, resulted from opposite cellular phenotypes. Cbfa1 overexpression caused acceleration of endochondral ossification due to precocious chondrocyte maturation, whereas overexpression of DN-Cbfa1 suppressed maturation and delayed endochondral ossification. In addition, Cbfa1 transgenic mice failed to form most of their joints and permanent cartilage entered the endochondral pathway, whereas most chondrocytes in DN-Cbfa1 transgenic mice retained a marker for permanent cartilage. These data show that temporally and spatially regulated expression of Cbfa1 in chondrocytes is required for skeletogenesis, including formation of joints, permanent cartilages, and endochondral bones.
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DOI：
10.1083/jcb.140.2.409
发表时间：
1998-01-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Enomoto-Iwamoto M;Iwamoto M;Mukudai Y;Kawakami Y;Nohno T;Higuchi Y;Takemoto S;Ohuchi H;Noji S;Kurisu K
通讯作者：
Kurisu K
影响因子：
6.9
作者：
Pacifici, M
通讯作者：
Pacifici, M
Osf2/Cbfa1：成骨细胞分化的转录激活因子
影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G
影响因子：
6.9
作者：
Pullig, O;Weseloh, G;Swoboda, B
通讯作者：
Swoboda, B
影响因子：
8
作者：
Sato, M;Morii, E;Nomura, S
通讯作者：
Nomura, S