Nicotinamide enhances osteoblast differentiation through the activation of mitochondrial antioxidant defense system

Abstract

Abstract Though the normal physiological level of oxidative stress is beneficial for maintaining bone homeostasis, however, the imbalance between reactive oxygen species (ROS) production and antioxidant defense can cause various bone diseases. The purpose of this study was to see whether nicotinamide (NAM), an NAD+ precursor, could support the maintenance of bone homeostasis via regulating osteoblasts. Here, we demonstrate that NAM enhanced osteoblast differentiation and mitochondrial metabolism. NAM increased the expression of antioxidant enzymes, which was due to increased FOXO3a transcriptional activity via SIRT3 activation. NAM has not only a preventive effect to a weak and chronic oxidative stress but also a therapeutic effect to a strong and acute exposure to H2O2 in osteoblasts differentiation. Collectively, NAM increased mitochondrial biogenesis and antioxidant enzyme expression through the activation of SIRT3-FOXO3a axis that consequently enhanced osteoblast differentiation. These results suggest NAM could be a potential preventive or therapeutic agent for the bone diseases caused by ROS.