Maimonides Institute for Biomedical Research (IMIBIC), 14004, Cordoba, Spain.
Nephrology Service, Reina Sofia University Hospital, 14004, Cordoba, Spain.
Sci Rep. 2017 Aug 10;7(1):7839. doi: 10.1038/s41598-017-08379-y.
Mesenchymal stem cells (MSC) are osteoblasts progenitors and a variety of studies suggest that they may play an important role for the health in the field of bone regeneration. Magnesium supplementation is gaining importance as adjuvant treatment to improve osteogenesis, although the mechanisms involving this process are not well understood. The objective of this study was to investigate the effects of magnesium on MSC differentiation. Here we show that in rat bone marrow MSC, magnesium chloride increases MSC proliferation in a dose-dependent manner promoting osteogenic differentiation and mineralization. These effects are reduced by 2-APB administration, an inhibitor of magnesium channel TRPM7. Of note, magnesium supplementation did not increase the canonical Wnt/β-catenin pathway, although it promoted the activation of Notch1 signaling, which was also decreased by addition of 2-APB. Electron microscopy showed higher proliferation, organization and maturation of osteoblasts in bone decellularized scaffolds after magnesium addition. In summary, our results demonstrate that magnesium chloride enhances MSC proliferation by Notch1 signaling activation and induces osteogenic differentiation, shedding light on the understanding of the role of magnesium during bone regeneration.
间充质干细胞（MSC）是成骨细胞的前体细胞，多种研究表明它们可能在骨再生领域的健康中发挥重要作用。镁补充剂作为辅助治疗方法越来越受到重视，以改善成骨作用，尽管涉及这一过程的机制尚不清楚。本研究的目的是研究镁对 MSC 分化的影响。在这里，我们表明在大鼠骨髓 MSC 中，氯化镁以剂量依赖的方式增加 MSC 的增殖，促进成骨分化和矿化。2-APB 的给药会降低这些作用，2-APB 是镁通道 TRPM7 的抑制剂。值得注意的是，镁补充并没有增加经典的 Wnt/β-连环蛋白途径，尽管它促进了 Notch1 信号的激活，而添加 2-APB 也会降低 Notch1 信号的激活。电子显微镜显示，在添加镁后，脱细胞骨支架中的成骨细胞增殖、组织和成熟度更高。总之，我们的结果表明，氯化镁通过 Notch1 信号的激活增强 MSC 的增殖，并诱导成骨分化，这为理解镁在骨再生过程中的作用提供了线索。
