Chu Ling, Jiang Yuehua, Hao Hong, Xia Yong, Xu Jian, Liu Zehao, Verfaillie Catherine M, Zweier Jay L, Liu Zhenguo
The Ohio State University Medical Center, Columbus, Ohio, USA.
Eur J Pharmacol. 2008 Sep 4;591(1-3):59-65. doi: 10.1016/j.ejphar.2008.06.066. Epub 2008 Jun 22.
This study was designed to investigate the role of nitric oxide (NO) in bone marrow stem cells and their differentiation into endothelial cells in vitro. Adult mouse bone marrow multipotent progenitor cells (MAPCs) were used as the source of stem cells. Oct-4 expression (both mRNA and protein) was significantly increased by up to 68.0% in MAPCs when incubated with NO donors DETA-NONOate or sodium nitroprusside (SNP) in a concentration-dependant manner (n=3, P<0.05). However, the cell proliferation was dramatically decreased by over 3-folds when treated with DETA-NONOate or SNP for 48 h (n=3, P<0.05). When MAPCs were exposed to DETA-NONOate (100 microM) for the first 48 h during differentiation, the expression (both mRNA and protein) of vWF was significantly increased at day 14 in the differentiating cells. The effects of DETA-NONOate or SNP on cell proliferation, Oct-4 expression and endothelial differentiation of MAPCs were not affected by the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or cGMP analog 8-Br-cGMP. These data indicate that NO may regulate both the pluripotency and differentiation of MAPCs via a cGMP-independent mechanism.
本研究旨在探讨一氧化氮（NO）在体外骨髓干细胞及其向内皮细胞分化过程中的作用。成年小鼠骨髓多能祖细胞（MAPCs）被用作干细胞来源。当与NO供体DETA-NO非诺酯或硝普钠（SNP）以浓度依赖性方式孵育时，MAPCs中Oct-4表达（mRNA和蛋白质）显著增加高达68.0%（n = 3，P < 0.05）。然而，用DETA-NO非诺酯或SNP处理48小时后，细胞增殖显著降低超过3倍（n = 3，P < 0.05）。当MAPCs在分化的前48小时暴露于DETA-NO非诺酯（100 microM）时，分化细胞在第14天vWF的表达（mRNA和蛋白质）显著增加。DETA-NO非诺酯或SNP对MAPCs细胞增殖、Oct-4表达和内皮分化的影响不受鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮或cGMP类似物8-Br-cGMP的影响。这些数据表明，NO可能通过一种不依赖cGMP的机制调节MAPCs的多能性和分化。
