BACKGROUND

Bone degenerative disorders like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Although there are studies suggesting that metabolic changes occur with stem cell differentiation, the molecular mechanisms governing energy metabolism and epigenetic modification are not understood fully. Here we reported the key role of nicotinamide phosphoribosyltransferase (Nampt), which is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide, in the osteogenic differentiation of bone marrow stromal cells.

RESULTS

Differentiated bone marrow stromal cells isolated from mice presented with diminished osteogenesis, as evaluated by alkaline phosphatase (ALP) staining, ALP activity and osteoblast-mediated mineralization, compared to cells from mice. Similar results were observed in differentiated Nampt-deficient C3H/10T1/2 and MC3T3-E1 cells. Further studies showed that Nampt promotes osteoblast differentiation through increased function and expression of as tested by luciferase reporter assay, RT-PCR, and Western Blotting. Our data also demonstrated that Nampt regulates transcription in part through epigenetic modification of H3-Lys9 acetylation.

CONCLUSION

Our study demonstrated that Nampt plays a critical role in osteoblast differentiation through epigenetic augmentation of transcription. NAMPT may be a potential therapeutic target of aging-related osteoporosis.