Magnesium promotes vascularized osseointegration in diabetic states

The poor osseointegration of dental implants in diabetic patients has become a long-standing clinical problem. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg2+ promotes vascularized osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants sucessfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg2+ promoted the degradation of Kelch-like ECH associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data proved that Mg2+ promoted vascularized osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism. HUVEC were cultured in three different conditions: high glucose (HG, 35mM), and HG+Mg2+ (MgSO4, MACKLIN).HUVECs were treated with HG medium or HG medium containing 5mM Mg2+ for 48h (n = 3 in each group) for RNA-Sequencing .Then we performed analysis and compared gene expression.