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

Abstract

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.

Dynamic proteomic profiling of human periodontal ligament stem cells during osteogenic differentiation

“…Emerging studies have discussed the functions of different sirtuins in the field of osteogenesis during the last decade. SIRT1 mediated the enhancement of osteogenic differentiation by exogenous antioxidants [76,77]. Upregulation of SIRT3 was found during the antioxidation by melatonin in osteogenesis along with strengthening the activity of SOD2 [78].…”

Effects of inhibiting PDK‑1 expression in bone marrow mesenchymal stem cells on osteoblast differentiation in vitro

“…Ascorbic acid may promote the synthesis of collagen I in cultured cells, and regulate ATP and ALP activity and the synthesis of non-collagen matrix proteins ( 37 ). β-glycerophosphate has been shown to provide phosphate ions to osteoblasts, and promote the deposition and calcification of physiological calcium salts, which is a necessary condition for mineralized nodules in BMSCs ( 38 ). When medium contains these components, BMSCs undergo a series of changes, resulting in them obtaining the morphology and growth characteristics of osteoblasts ( 39 ).…”

Role of PGC-1α in the Mitochondrial NAD+ Pool in Metabolic Diseases

“…NR can also be used as a precursor for NMN by NR kinase (NRK) in the salvage pathway [ 52 ]. A few studies have revealed that PGC-1α is closely linked to the NAD + salvage pathway ( Figure 1 ), and metabolites in the NAD + salvage pathway, such as NR and NMN, have been shown to upregulate the SIRT1–PGC-1α pathway in the liver [ 36 ] and bone [ 53 ]. Moreover, NAMPT is a rate-limiting enzyme responsible for the conversion of NAD + in the salvage pathway [ 54 , 55 ] and is associated with PGC-1α to generate NAD + in the renal epithelium [ 18 ] and regulates mitochondrial biogenesis via NAD metabolism in the skeletal muscle [ 56 ].…”

“…However, further studies are required to understand the relationship between NAMPTs and PGC-1α in the NAD + salvage pathway in various tissues. NMN treatment has also been shown to alleviate osteogenic inhibition and promote the expression of SIRT1 and PGC-1α, whereas these beneficial effects of NMN were reversed when SIRT1 and PGC-1α were decreased [ 53 ]. Thus, the SIRT1–PGC-1α pathway may be involved in the conversion of NMN into NAD + ; however, the mechanism by which SIRT1–PGC-1α regulates NMNAT to convert NMN into NAD + is still poorly understood.…”

“…There are few studies on the relationship between PGC-1α and the Preiss–Handler pathway; however, NMNATs are also involved in this pathway to catalyze NAMN in NAAD [ 57 ]. Since PGC-1α possibly influences NMNATs that partially catalyze NMN to NAD + in the salvage pathway [ 53 , 58 ], PGC-1α is likely to be involved in the functioning of NMNATs in the Preiss–Handler pathway as well.…”