Qu Zhi-Hu, Zhang Xiao-Ling, Tang Ting-Ting, Dai Ke-Rong
Orthopaedic Cellular and Molecular Biology Laboratory, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai JiaoTong University School of Medicine, Shanghai, China.
Biochem Biophys Res Commun. 2008 May 30;370(2):332-7. doi: 10.1016/j.bbrc.2008.03.092. Epub 2008 Mar 28.
Desferrioxamine, an iron chelator with "hypoxia-mimetic" activity, promotes bone mineralization when used in aluminum-overloaded dialysis patients. However, the effect of desferrioxamine on osteoblastic differentiation from pluripotent mesenchymal stem cells (MSCs) has not been reported. In this study, pluripotent human MSCs and murine mesenchymal C3H10T1/2 cells were simultaneously treated with desferrioxamine and bone morphogenetic protein-2 (BMP2). In BMP2-treated MSCs, desferrioxamine levels of 15 microMu were found to increase alkaline phosphatase (ALP) activity and calcium deposition, which were the markers of osteoblastic differentiation. These effects of desferrioxamine were accompanied by promoted phosphorylation of glycogen synthase kinase 3beta (GSK-3beta) and increased beta-catenin protein content, a direct GSK-3beta substrate. Knockdown of beta-catenin by RNA interference eliminates this positive effect of desferrioxamine on ALP activity. Taken together, these data demonstrate that desferrioxamine plays a direct role in the differentiation of mesenchymal stem cells by activating beta-catenin signaling cascades.
去铁胺是一种具有“缺氧模拟”活性的铁螯合剂，在铝过载的透析患者中使用时可促进骨矿化。然而，去铁胺对多能间充质干细胞（MSC）向成骨细胞分化的影响尚未见报道。在本研究中，将多能人类MSC和小鼠间充质C3H10T1/2细胞同时用去铁胺和骨形态发生蛋白-2（BMP2）处理。在BMP2处理的MSC中，发现15微摩尔的去铁胺水平可增加碱性磷酸酶（ALP）活性和钙沉积，这是成骨细胞分化的标志物。去铁胺的这些作用伴随着糖原合酶激酶3β（GSK-3β）磷酸化的促进和β-连环蛋白含量的增加，β-连环蛋白是GSK-3β的直接底物。通过RNA干扰敲低β-连环蛋白可消除去铁胺对ALP活性的这种积极作用。综上所述，这些数据表明去铁胺通过激活β-连环蛋白信号级联在间充质干细胞的分化中起直接作用。
