Magnesium–Magnetic Field Synergy Enhances Mouse Bone Marrow Mesenchymal Stem Cell Differentiation into Osteoblasts Via the MAGT1 Channel

Abstract

Magnesium ion (Mg2+)-based materials are known to exert osteogenic effects that can be enhanced by the bioelectrical properties of magnetic fields. In this study, we examined the effect of a medium-strength static magnetic field (SMF), combined with a Mg2+-containing medium, on the proliferation and osteogenic differentiation of mouse bone marrow mesenchymal stem cells (BMSCs). Mouse BMSCs were divided into a control group, 7.5 mM Mg2+ group, 15 mT SMF group, and 7.5 mM Mg2+ plus 15 mT SMF group. Osteoblast proliferation was measured using a Cell Counting Kit-8 assay, whereas osteogenic differentiation was detected using alkaline phosphatase (ALP) staining and western blot analysis, respectively. The number and size of calcium nodules were determined using Alizarin Red staining. Compared with those in the control group, the ALP activity, calcium nodule formation, and osteogenic protein expression were promoted in other groups. In particular, Mg2+-SMF had a significant effect after 7 days of intervention and more effectively promoted BMSC differentiation and proliferation than either Mg2+ or the SMF alone, suggesting that Mg2+-SMF synergistically contributed to osteogenic differentiation and cell proliferation. To examine their roles in bone differentiation, the Magt1 and Creb1 genes were silenced in BMSCs, and the findings indicated that the synergistic intervention with Mg2+ and magnetic fields might exert osteogenic effects via the MAGT1 channel and CREB1 protein. This study provides an experimental basis for a potential Mg2+-SMF synergistic artificial bone material that could be clinically applied in the treatment of bone defects.

Static magnetic field enhances the bone remodelling capacity of human demineralized bone matrix in a rat animal model of cranial bone defects

“…It was discovered that this combination significantly improved osteogenic differentiation and cell proliferation, perhaps through the CREB1 protein and MAGT1 channel. 54 Furthermore, higher levels of osteogenesis-related proteins such as ALP, Collagen I, Osteopontin, and Osteocalcin have been observed in both in vitro and in vivo after exposure to an external MF. 55…”

The development of magnesium‐based biomaterials in bone tissue engineering: A review

“…These processes can induce the expression of intracellular osteogenic signaling molecules alkaline phosphatase (ALP), collagen type I (COL1), and Runt-related transcription factor 2 (RUNX2). [20][21][22] First, Mg 2+ can promote the osteogenic differentiation of MSCs by different signaling pathways. For example, the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway can be activated through MagT1.…”

“…F I G U R E 2 Illustration scheme of the osteogenic mechanism of Mg. Mg 2+ enters cells through many transporters such as MagT1 and TRPM6/7 and actives MAPK/ERK signal pathway, Wnt/β-catenin signaling, and PI3K/Akt signal pathway to promote osteogenesis and angiogenesis. [19][20][21][22][23][24][25][26][27][28][29] In addition, Mg 2+ can stimulate the expression of BMP-2 in macrophages, which acts as the signal molecule in MSCs to promote osteogenic differentiation. [30][31][32] MAPK/ERK, mitogen-activated protein kinase/ extracellular regulated kinase; MSC, mesenchymal stem cell; TRPM6/7, transient receptor potential melastatin type 6/7.…”

“…Illustration scheme of the osteogenic mechanism of Mg. Mg 2+ enters cells through many transporters such as MagT1 and TRPM6/7 and actives MAPK/ERK signal pathway, Wnt/β‐catenin signaling, and PI3K/Akt signal pathway to promote osteogenesis and angiogenesis 19–29 . In addition, Mg 2+ can stimulate the expression of BMP‐2 in macrophages, which acts as the signal molecule in MSCs to promote osteogenic differentiation 30–32 .…”

“…Studies have demonstrated that MagT1 and TRPM6/7 have the functional duality of an ion channel and a kinase to promote osteogenic differentiation. These processes can induce the expression of intracellular osteogenic signaling molecules alkaline phosphatase (ALP), collagen type I (COL1), and Runt‐related transcription factor 2 (RUNX2) 20–22 …”