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

Abstract

Although the normal physiological level of oxidative stress is beneficial for maintaining bone homeostasis, imbalance between reactive oxygen species (ROS) production and antioxidant defense can cause various bone diseases. The purpose of this study was to determine whether nicotinamide (NAM), an NAD(+) precursor, can support the maintenance of bone homeostasis by regulating osteoblasts. Here, we found that NAM enhances osteoblast differentiation and mitochondrial metabolism. NAM increases the expression of antioxidant enzymes, which is due to increased FOXO3A transcriptional activity via SIRT3 activation. NAM has not only a preventive effect against weak and chronic oxidative stress but also a therapeutic effect against strong and acute exposure to H2O2 in osteoblast differentiation. Collectively, the results indicate that NAM increases mitochondrial biogenesis and antioxidant enzyme expression through activation of the SIRT3-FOXO3A axis, which consequently enhances osteoblast differentiation. These results suggest that NAM could be a potential preventive or therapeutic agent for bone diseases caused by ROS. Bone health: Vitamin B3 boosts anti-oxidantsA form of vitamin B3 called nicotinamide (NAM) has potential to prevent or treat bone diseases related to oxidative stress by boosting production of anti-oxidant enzymes. Mitochondria, the powerhouses of the cell, produce reactive oxygen species (ROS) during normal metabolism. If these ROS are not countered by enough anti-oxidants, oxidative stress can decrease production of bone-building cells called osteoblasts, leading to bone aging and osteoporosis. Hyun-Mo Ryoo and Woo-Jin Kim at Seoul National University in South Korea and co-workers investigated whether NAM, the precursor of a key mitochondrial molecule, could restore ROS balance. In experiments in bone cells, NAM improved mitochondrial function, boosted anti-oxidant production, and promoted osteoblast formation. NAM prevented and repaired oxidative damage in bone cells and therefore shows potential both as a preventative and therapeutic treatment for bone health.