Magnesium enhances the chondrogenic differentiation of mesenchymal stem cells by inhibiting activated macrophage-induced inflammation

Magnesium deficiency increases the generation of pro-inflammatory cytokines, which is consistently accompanied by the sensitization of cells such as neutrophils, macrophages and endothelial cells. We investigated the potential of magnesium to regulate macrophage polarization and macrophage-induced inflammation with or without lipopolysaccharide (LPS) and interferon-γ (IFN-γ) activation and further elucidated whether these effects impact the inhibitory functions of activated macrophage-induced inflammation on cartilage regeneration. The results showed that magnesium inhibited the activation of macrophages, as indicated by a significant reduction in the percentage of CCR7-positive cells, while the percentage of CD206-positive cells decreased to a lesser degree. After activation, both pro-inflammatory and anti-inflammatory cytokines were down-regulated at the mRNA level and certain cytokines (IL-1β, IL-6 and IL-10) were decreased in the cell supernatant with the addition of magnesium. Moreover, magnesium decreased the nuclear translocation and phosphorylation of nuclear factor-κB (NF-κB) to impede its activation. A modified micromass culture system was applied to assess the effects of activated macrophage-conditioned medium with or without magnesium treatment on the chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Magnesium enhanced the chondrogenic differentiation of hBMSCs by reversing the adverse effects of activated macrophage-induced inflammation.