A Cerium Oxide Loaded Hyaluronic Acid Nanosystem Remits Glucose Oxidative Stress-Induced Odontoblasts Mitochondrial Apoptosis through Regulation of PGAM5 Pathway

Diabetes mellitus (DM) induced mitochondrial oxidative stress (OS) can lead to severe injury of dental pulp. The cerium oxide nanoparticles (CNP) have been proven to have excellent antioxidative activity. However, whether CNP can relieve dental pulp damage caused by DM and the underlying mechanisms remain unclear. In this study, we modified ceria with hyaluronic acid to prepare nanoceria with good biocompatibility, water solubility, and stability, namely, HACNP (hyaluronic acid cerium oxide nanoparticles). We demonstrated the protective effect of HACNP on diabetic OS-induced mitochondrial apoptosis in dental pulp-like cells. As far as the mechanism of action was concerned, glucose oxidase (GO) treatment promoted the activation of phosphoglycerate mutase family 5 (PGAM5) leading to mitochondrial abnormalities and apoptosis in an odontoblast-like cell line (mDPC6T). Knockdown or overexpression of PGAM5 further validate these results. Meanwhile, HACNP remitted GO-related toxicity via down-regulating PGAM5 expression, whereas overexpression of PGAM5 abolished the beneficial effect of HACNP. Furthermore, in the constructed animal research model of diabetic pulp injury, we also confirmed that HACNP alleviated apoptosis and mitochondrial injury of dental pulp and decreased the expression level of PGAM5 in diabetic pulp tissue. In conclusion, these results revealed that HACNP played a protective role on diabetes-associated dental pulp injury through targeting the PGAM5-mediated mitochondrial pathway, providing an idea and method for the prevention or treatment of diabetes-induced dental pulp damage.