BMP-2 Induced Expression of Alx3 That Is a Positive Regulator of Osteoblast Differentiation.
BMP-2 Induced Expression of Alx3 That Is a Positive Regulator of Osteoblast Differentiation.
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BMP-2诱导的ALX3表达是成骨细胞分化的阳性调节剂。
DOI：
10.1371/journal.pone.0068774
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kamijo R
中科院分区：
文献类型：
--
作者：
Matsumoto T;Yamada A;Aizawa R;Suzuki D;Tsukasaki M;Suzuki W;Nakayama M;Maki K;Yamamoto M;Baba K;Kamijo R
骨形态发生蛋白（BMP）调节骨骼发育的许多方面，包括成骨细胞和软骨细胞分化，软骨和骨形成，以及颅骨和肢体发育。其中，BMP-2，最有效的成骨信号分子之一，刺激成骨细胞分化，而它抑制C2 C12细胞的成肌分化。为了评估BMP-2诱导成骨细胞分化的基因，我们进行了cDNA微阵列分析，比较BMP-2处理和未处理的C2 C12细胞。我们专注于Alx 3（aristaless-like homeobox 3），它在成骨细胞分化过程中明显被诱导。Alx 3，一个与肿瘤相关的同源框基因， 果蝇无芒基因与颅面结构和肢体发育有关。然而，很少有人知道它与骨形成的直接关系。本研究旨在探讨Alx 3基因在BMP-2诱导成骨细胞分化过程中的表达及功能机制。在C2 C12细胞中，BMP-2通过BMP受体介导的SMAD信号通路以时间和剂量依赖性方式诱导Alx 3基因表达增加。此外，通过siRNA沉默Alx 3抑制BMP-2诱导的成骨细胞分化，如碱性磷酸酶（Alp）、骨钙素和Osterix的表达所示，而Alx 3的过表达增强BMP-2诱导的成骨细胞分化。这些结果表明，BMP-2通过BMP受体介导的Smad信号增强Alx 3表达，并且Alx 3是BMP-2诱导的成骨细胞分化的正调节剂。
Bone morphogenetic proteins (BMPs) regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP-2, one of the most potent osteogenic signaling molecules, stimulates osteoblast differentiation, while it inhibits myogenic differentiation in C2C12 cells. To evaluate genes involved in BMP-2-induced osteoblast differentiation, we performed cDNA microarray analyses to compare BMP-2-treated and -untreated C2C12 cells. We focused on Alx3 (aristaless-like homeobox 3) which was clearly induced during osteoblast differentiation. Alx3, a homeobox gene related to the Drosophila aristaless gene, has been linked to developmental functions in craniofacial structures and limb development. However, little is known about its direct relationship with bone formation. In the present study, we focused on the mechanisms of Alx3 gene expression and function during osteoblast differentiation induced by BMP-2. In C2C12 cells, BMP-2 induced increase of Alx3 gene expression in both time- and dose-dependent manners through the BMP receptors-mediated SMAD signaling pathway. In addition, silencing of Alx3 by siRNA inhibited osteoblast differentiation induced by BMP-2, as showed by the expressions of alkaline phosphatase (Alp), Osteocalcin, and Osterix, while over-expression of Alx3 enhanced osteoblast differentiation induced by BMP-2. These results indicate that Alx3 expression is enhanced by BMP-2 via the BMP receptors mediated-Smad signaling and that Alx3 is a positive regulator of osteoblast differentiation induced by BMP-2.
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影响因子：
4.8
作者：
Zhao, Baohong;Katagiri, Takenobu;Kamijo, Ryutaro
通讯作者：
Kamijo, Ryutaro
影响因子：
4.1
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Vallejo, Mario
影响因子：
64.5
作者：
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通讯作者：
de Crombrugghe, B
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4.8
作者：
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通讯作者：
Tezuka, K
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4.8
作者：
Hassan, Mohammad Q.;Tare, Rahul S.;Lian, Jane B.
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Lian, Jane B.