The polycomb group (PcG) protein enhancer of zeste homologue 2 (Ezh2), a histone lysine methyltransferase is associated with epigenetic regulation of numerous cellular processes, it is not yet clear on its involvement in bone cell development and homeostasis. Conditional deletion of Ezh2 in macrophages resulted in significant increases in postnatal bone growth in the first 6 months of life, but tibia length and body weight gains were not different in knockout mice compared with their wild type controls. Significantly decreased osteoclastogenesis but increased bone mass without osteopetrosis were found in Ezh2 CKO mice. In contrast to female mice, one floxed Ezh2 gene copy recombinant with LysM-Cre+ (Ezh2flox/+LysM-Cre+) produced increased bone mass in young adult male mice compared with control mice (Ezh2flox/flox, LysM-Cre+ and wild type). Deletion of Ezh2 in macrophages triggered increased gene expression of osteoclast suppressors, IRF8, MafB and Arg1 due to decreased Ezh2-induced trimethylation of H3K27me3. These findings suggest that pre-osteoclastic cell differentiation is under epigenetic control of osteoclast suppressive gene expression via an Ezh2-dependent mechanisms.
Osteocytic oxygen sensing controls bone mass through epigenetic regulation of sclerostin