High-throughput screening was performed as a phenotypic screening on clinically relevant human mesenchymal stem cells to identify small molecules that affect stem cell fate. From a library of pharmacologically active small molecules, we identified kaempferol, which is a natural flavonol, with a high osteogenic activity. Kaempferol achieved the highest levels of bone-specific markers among the chemicals tested in vitro. The osteogenic activity of kaempferol was the same as that of ipriflavone, which is a synthetic isoflavone, in ovariectomized mouse experiments. Considering that kaempferol is present in various foods such as vegetables and fruits, it will be useful as a new preventive medicine for osteoporosis. (C) 2013 Elsevier Ltd. All rights reserved.