Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1

被引:35
|
作者
Katsuki, Yuko [1 ,2 ]
Sakamoto, Kel [1 ]
Minamizato, Tokutaro [1 ]
Makino, Hatsune
Umezawa, Akihiro [3 ]
Ikeda, Masa-Aki [1 ]
Perbal, Bernard [4 ]
Amagasa, Teruo [2 ]
Yamaguchi, Akira
Katsube, Ken-Ichi [1 ]
机构
[1] Tokyo Med & Dent Univ, Grad Sch, Bunkyo Ku, Tokyo 1138549, Japan
[2] Tokyo Med & Dent Univ, Grad Sch, Tokyo, Japan
[3] NICHHD, Dept Reprod Biol, Tokyo, Japan
[4] Univ Paris 7 D Diderot, Lab Oncol Virale & Mol, Paris, France
基金
日本学术振兴会;
关键词
CCN3; NOV; Notch; p21; osteogenesis; BMP;
D O I
10.1016/j.bbrc.2008.02.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CCN3/NOV activates the Notch signal through the carboxyl terminal cysteine-rich (CT) domain. CCN3 transfection to Kusa-A1 inhibited osteogenic differentiation and cell proliferation, which is accompanied by upregulation of Hes/Hey, Notch downstream targets, and p21, a CDK inhibitor. Upregulation of Hes/Hey and p21 was abrogated by the deletion of CT domain. Anti-proliferative activity of CCN3 was also abrogated by CT domain deletion whereas anti-osteogenic activity was not completely abrogated. We found that CT domain-deleted CCN3 still possesses antagonistic effect on BMP-2. These results suggest that CCN3 employs Notch and BMP pathways in anti-osteogenic activity while it inhibits cell proliferation uniquely by Notch/p21 pathway. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:808 / 814
页数:7
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