Recent Advance in Epigenetics - Application to The Regulation of Osteoclast Differentiation

Osteoclasts are primary cells for bone resorption, and their differentiation is tightly regulated by receptor activator of nuclear factor kappa B ligand (RANKL) and a transcription factor nuclear factor-activated T cells (NFAT) c1. Recent studies have uncovered that the epigenetic regulation such as DNA methylation, histone methylation and acetylation, and micro RNAs play a critical role in cell differentiation. In particular, the expression of key developmental genes tends to be tightly regulated by trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3). Several reports have been proposed regarding the epigenetic regulation of osteoclast differentiation including this specific histone modification change. RANKL-induced NFATc1 expression is associated with the demethylation of H3K27me3 in osteoclast precursors. Jumonji domain containing-3 (Jmjd3), a H3K27 demethylase, is induced in murine bone marrow-derived macrophages in response to RANKL stimulation, and supposedly plays a critical role in the demethylation of H3K27me3 in the Nfatc1 gene and osteoclast differentiation.