Nampt expression increases during osteogenic differentiation of multi- and omnipotent progenitors

Abstract

Despite emerging data showing that metabolic changes occur with stem cell differentiation, the cross-talk between factors governing energy metabolism and epigenetic modification is not understood. Nicotinamide adenine dinucleotide (NAD) participates in both energy metabolism and protein modification processes. Changes of the intracellular NAD concentration have been shown to correlate with differentiation of adult and embryonic stem cells. In the present study, we investigated the expression pattern of Nampt, the rate-limiting enzyme in NAD salvaging pathway, during osteogenic differentiation of the multipotent mouse fibroblast C3H10T1/2 and the omnipotent preosteoblast MC3T3-E1 cells. We found that Nampt was increasingly expressed during differentiation in both cell models. The increase of Nampt was associated with higher NAD concentration and Sirt1 activity. Knockdown of Nampt or addition of its specific inhibitor FK866 leads to lower intracellular NAD concentration and decline in osteogenesis. These findings indicate that osteogenic differentiation correlates with intracellular NAD metabolism in which Nampt plays a regulatory role.