Nicotinamide mononucleotide attenuates glucocorticoid-induced osteogenic inhibition by regulating the SIRT1/PGC-1α signaling pathway

Long-term and high-dose glucocorticoid treatment is recognized as an important influencing factor for osteoporosis and osteonecrosis. Nicotinamide mononucleotide (NMN) is an intermediate of NAD(+) biosynthesis, and is widely used to replenish the levels of NAD(+). However, the potential role of NMN in glucocorticoid-induced osteogenic inhibition remains to be demonstrated. In the present study, the protective effects of NMN on dexamethasone (Dex)-induced osteogenic inhibition, and its underlying mechanisms, were investigated. Bone mesenchymal stem cells were treated with Dex, which decreased the levels of the osteogenic markers alkaline phosphatase, Runt-related transcription factor 2 and osteocalcin. NMN treatment attenuated Dex-induced osteogenic inhibition and promoted the expression of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α. SIRT1 knockdown reversed the protective effects of NMN and reduced the expression levels of PGC-1α. Collectively, the results of the present study reveal that NMN may be a potential therapeutic target for glucocorticoid-induced osteoporosis.