Katsuki Yuko, Sakamoto Kei, Minamizato Tokutaro, Makino Hatsune, Umezawa Akihiro, Ikeda Masa-Aki, Perbal Bernard, Amagasa Teruo, Yamaguchi Akira, Katsube Ken-Ichi
Maxillofacial Surgery, Graduate School of Tokyo Medical and Dental University, Tokyo, Japan.
Biochem Biophys Res Commun. 2008 Apr 11;368(3):808-14. doi: 10.1016/j.bbrc.2008.02.010. Epub 2008 Feb 12.
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.
CCN3/NOV通过富含半胱氨酸的羧基末端（CT）结构域激活Notch信号。将CCN3转染至Kusa - A1细胞可抑制成骨分化和细胞增殖，同时伴有Notch下游靶点Hes/Hey以及细胞周期蛋白依赖性激酶抑制剂p21的上调。Hes/Hey和p21的上调可通过缺失CT结构域而消除。CT结构域缺失也消除了CCN3的抗增殖活性，而抗成骨活性并未完全消除。我们发现缺失CT结构域的CCN3对BMP - 2仍具有拮抗作用。这些结果表明，CCN3在抗成骨活性中利用了Notch和BMP信号通路，而它仅通过Notch/p21信号通路抑制细胞增殖。
