CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways
CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways
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DOI：
10.1016/j.bbrc.2007.01.029
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发表时间：
2007-03-09
影响因子：
3.1
通讯作者：
Yamaguchi, Akira
中科院分区：
文献类型：
--
作者：
Minamizato, Tokutaro;Sakamoto, Kei;Yamaguchi, Akira
我们阐明了CCN 3/NOV，CCN家族蛋白的成员，在成骨细胞分化中使用MC 3 T3-E1成骨细胞的作用。单独用CCN 3腺病毒（AdCCN 3）转导不会引起成骨细胞相关标志物表达的明显变化，而用BMP-2腺病毒（AdBMP-2）和AdCCN 3共同转导显着抑制AdBMP-2诱导的Runx 2、osterix、ALP和骨钙素mRNA表达。免疫沉淀-Western分析显示CCN 3与BMP-2相关。与单独用AdBMP-2转导相比，用AdBMP-2和AdCCN 3共转导减弱了磷酸化Smad 1/5/8和Id 1、M2和M3的mRNA的表达。用AdCCN 3转导刺激切割的Notch 1的表达、Hes 1和Hey 1/Hesr 1的mRNA表达以及Hes 1和Hey 1的启动子活性。CCN 3对BMP-2诱导的成骨细胞相关标志物表达的抑制作用在Hey 1缺陷的成骨细胞中被抵消。这些结果表明，CCN 3通过其参与BMP和Notch信号通路对BMP-2诱导的成骨细胞分化发挥抑制作用。(c)2007爱思唯尔公司All rights reserved.
We elucidate the role of CCN3/NOV, a member of the CCN family proteins, in osteoblast differentiation using MC3T3-E1 osteoblastic cells. Transduction with CCN3 adenovirus (AdCCN3) alone induced no apparent changes in the expression of osteoblast-related markers, whereas cotransduction with BMP-2 adenovirus (AdBMP-2) and AdCCN3 significantly inhibited the AdBMP-2-induced mRNA expression of Runx2, osterix, ALP, and osteocalcin. Immunoprecipitation-western analysis revealed that CCN3 associated with BMP-2. Compared to transduction with AdBMP-2 alone, cotransduction with AdBMP-2 and AdCCN3 attenuated the expression of phosphorylated Smad1/5/8 and the mRNA for Id1, M2, and M3. Transduction with AdCCN3 stimulated the expression of cleaved Notch1, the mRNA expression of Hes1 and Hey1/Hesr1, and the promoter activities of Hes1 and Hey1. The inhibitory effects of CCN3 on the expression of BMP-2-induced osteoblast-related markers were nullified in Hey1-deficient osteoblastic cells. These results indicate that CCN3 exerts inhibitory effects on BMP-2-induced osteoblast differentiation by its involvement of the BMP and Notch signaling pathways. (c) 2007 Elsevier Inc. All rights reserved.