Runx2 alleviates high glucose‐suppressed osteogenic differentiation via PI3K/AKT/GSK3β/β‐catenin pathway

Abstract Hyperglycemia is one of the most important pathogenesis of diabetic osteopathy. Several lines of studies indicate Runx2 plays a critical role in the process of osteogenic differentiation. However, little studies have analyzed the effect of Runx2 on osteoblast differentiation of rat bone mesenchymal stem cells (rBMSCs) in high‐glucose condition. In this study, the effect of Runx2 on osteoblast differentiation in high‐glucose condition was evaluated by the expression of osteogenesis‐related maker including Runx2, ALP, OC, and OPN, as well as ALP staining, ALP activity, and Alizarin red S staining. Western blot analysis was performed to detect the protein expression levels of p‐AKT, AKT, p‐GSK3β, GSK3β, and β‐catenin. Immunofluorescence staining analysis was performed to detect subcellular localization of β‐catenin. Our results revealed that high glucose significantly inhibited osteogenic differentiation, hyperosmolarity did not cause a suppression. In addition, Runx2 could upregulate the expression of osteogenic‐related genes and increase matrix mineralization, while applying 10 µM PI3K/AKT inhibitor LY294002 abolished the beneficial effect. Collectively, these results indicate that Runx2 alleviates high glucose‐induced inhibition of osteoblast differentiation by modulating PI3K/AKT/GSK3β/β‐catenin pathway.