Epigenetic regulation of osteoclast differentiation.

Recent studies have uncovered that epigenetic regulation, such as histone methylation and acetylation, plays a critical role in determining cell fate. In particular, the expression of key developmental genes tends to be regulated by trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3). Osteoclasts are primary cells for bone resorption, and their differentiation is tightly regulated by the receptor activator of nuclear factor κB ligand (RANKL) and a transcription factor nuclear factor-activated T cell (NFAT) c1. We found that RANKL-induced NFATc1 expression is associated with the demethylation of H3K27me3. Jumonji domain containing-3, a H3K27 demethylase, is induced in bone marrow-derived macrophages in response to RANKL stimulation and may play a critical role in the demethylation of H3K27me3 in the Nfatc1 gene.