Nicotinamide phosphoribosyltransferase (Nampt) affects the lineage fate determination of mesenchymal stem cells: a possible cause for reduced osteogenesis and increased adipogenesis in older individuals.

摘要: Human aging is associated with a progressive decline in bone mass and an accumulation of marrow fat. We found that osteoblast differentiation was reduced adipocyte formation increased stromal cells derived from aged mice compared young controls. The adipogenesis correlated relatively lower Sirt1 activity intracellular NAD+ concentration. suppose these effects were caused by age-related reduction nicotinamide phosphoribosyltransferase (Nampt), the enzyme catalyzing NAD resynthesis (NAM). In support this hypothesis, treatment Nampt inhibitor FK866 mineralization primary cultured cells. addition, knockdown mouse mesenchymal cell line C3H10T1/2 cells resulted decreased enhanced adipogenesis. Interestingly, although deficiency both NAM, could be controlled only regulation NAM. These results indicate lineage fate determination stem (MSCs) influenced energy metabolism points to possible mechanism for development senile osteoporosis. Furthermore, we suggest side on should considered when evaluating long-term safety NAD-interfering pharmaceuticals. © 2011 American Society Bone Mineral Research