Abstract
As the second most abundant intracellular cation, magnesium exists mostly in bone and the amount of magnesium is dynamically regulated by skeletal remodeling. Previous studies showed that accelerating bone mass loss occurs in post-menopause animals when their magnesium intake is insufficient and increased magnesium intake alleviates the osteoporotic symptoms. However, high magnesium status has been reported to lead to mineralization defects possibly due to the magnesium substitution for calcium in hydroxyapatite structure. In the present study, we used murine and human mesenchymal stromal cells (MSCs) to investigate the effect of high extracellular magnesium concentration on osteogenic differentiation and the role of magnesium transporters in the mineralization process. We verified the differentiation efficiency by observing cell morphology, expression profiling of osteogenic marker genes, and performing alizarin red staining (Fig. 1) . The results showed that high concentration of extracellular magnesium ion inhibited mineralization during osteogenic differentiation of MSCs. Gene expressions of osterix, type I collagen alpha 1, and alkaline phosphatase were downregulated, as well as osteopontin and osteocalcin were upregulated in MSCs treated with high concentration of magnesium. siRNA treatment targeting the specific magnesium transporter, which is also a member of solute carrier family SLC41, accelerated the mineralization process and ameliorated the inhibition of mineralization caused by high concentration of magnesium. The sensitivity to extracellular magnesium was also diminished after the knockdown. Pathway analysis of differentially expressed genes indicated that Wnt signaling is involved in the regulation mediated by the magnesium transporter. The study suggests that caution should be taken when magnesium supplement used as a therapy for bone mass loss and provide insights into the design of magnesium alloys for implantation.
Published Version
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