Inoue K, et al. – Clarification of the mechanisms underlying osteoclast differentiation enables us to understand the physiology of bone metabolism as well as the pathophysiology of bone diseases such as osteoporosis. Recently, it has been reported that epigenetics can determine cell fate and regulate cell type–specific gene expression. However, little is known about epigenetics during osteoclastogenesis. This study may reveal underlying mechanisms that determine cell type–specific differentiation of bone cells and may lead to investigate novel therapeutic targets for osteoporosis.