RT Journal Article T1 Magnesium Chloride promotes Osteogenesis through Notch signaling activation and expansion of Mesenchymal Stem Cells. A1 Diaz-Tocados, Juan M A1 Herencia, Carmen A1 Martinez-Moreno, Julio M A1 Montes de Oca, Addy A1 Rodriguez-Ortiz, Maria E A1 Vergara, Noemi A1 Blanco, Alfonso A1 Steppan, Sonja A1 Almaden, Yolanda A1 Rodriguez, Mariano A1 Muñoz-Castañeda, Juan R AB 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. PB Nature Publishing Group YR 2017 FD 2017-07-10 LK http://hdl.handle.net/10668/11496 UL http://hdl.handle.net/10668/11496 LA en NO Díaz-Tocados JM, Herencia C, Martínez-Moreno JM, Montes de Oca A, Rodríguez-Ortiz ME, Vergara N, et al. Magnesium Chloride promotes Osteogenesis through Notch signaling activation and expansion of Mesenchymal Stem Cells. Sci Rep. 2017 Aug 10;7(1):7839 NO We acknowledge the technical support provided by Esther Peralbo in performing the studies with Confocal Microscopy (IMIBIC). N Vergara and JM Díaz-Tocados are supported by Consejería de Economía, Innovación, Ciencia y Empleo from Junta de Andalucía (CVI-7925). ME Rodriguez-Ortiz is recipient of a “Sara Borrell” research contract from the National Institute of Health Carlos III. Y. Almaden and JR. Muñoz-Castañeda are senior researchers supported by Nicolás Monardes Programme, Consejeria de Salud-SAS (Junta de Andalucia). DS RISalud RD May 11, 2025