| Literature DB >> 27183582 |
Celestia Fang1, Yu Qiao1, Kyung-Hyun Park-Min1,2, Lionel B Ivashkiv1,2,3, Se Hwan Mun1, Min Joon Lee1, Koichi Murata1, Seyeon Bae1, Baohong Zhao1,2.
Abstract
Osteoclasts are resorptive cells that are important for homeostatic bone remodeling and pathological bone resorption. Emerging evidence suggests an important role for epigenetic mechanisms in osteoclastogenesis. A recent study showed that epigenetic silencing of the negative regulator of osteoclastogenesis Irf8 by DNA methylation is required for osteoclast differentiation. In this study, we investigated the role of EZH2, which epigenetically silences gene expression by histone methylation, in osteoclastogenesis. Inhibition of EZH2 by the small molecule GSK126, or decreasing its expression using antisense oligonucleotides, impeded osteoclast differentiation. Mechanistically, EZH2 was recruited to the IRF8 promoter after RANKL stimulation to deposit the negative histone mark H3K27me3 and downregulate IRF8 expression. GSK126 attenuated bone loss in the ovariectomy mouse model of postmenopausal osteoporosis. Our findings provide evidence for an additional mechanism of epigenetic IRF8 silencing during osteoclastogenesis that likely works cooperatively with DNA methylation, further emphasizing the importance of IRF8 as a negative regulator of osteoclastogenesis.Entities:
Mesh：
Substances：
Year: 2016 PMID： 27183582 PMCID： PMC4875854 DOI： 10.4049/jimmunol.1501466
Source DB: PubMed Journal: J Immunol ISSN： 0022-1767 Impact factor: 5.422