Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1
Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A1
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DOI：
10.1016/j.bbrc.2008.02.010
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发表时间：
2008-04-11
影响因子：
3.1
通讯作者：
Katsube, Ken-Ichi
中科院分区：
文献类型：
--
作者：
Katsuki, Yuko;Sakamoto, Kel;Katsube, Ken-Ichi
CCN3/Nov通过富含半胱氨酸的羧基末端结构域激活Notch信号。CCN3对Kusa-A1细胞的成骨分化和细胞增殖有抑制作用，并伴随着Hes/Hey、Notch下游靶点和CDK抑制物p21的上调。CT结构域的缺失取消了Hes/Hey和p21基因的上调。CCN3的抗增殖活性也通过CT结构域的缺失而被取消，但抗骨生成活性并未完全被取消。我们发现CT结构域缺失的CCN3对BMP-2仍有拮抗作用。这些结果表明，CCN3通过Notch和BMP途径发挥抗骨作用，而CCN3通过Notch/p21途径独特地抑制细胞增殖。(C)2008 Elsevier Inc.保留所有权利。
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.