Chin J Dent Res 21 (2018), No. 2 28. June 2018
Chin J Dent Res 21 (2018), No. 2 (28.06.2018)
Page 113-118, doi:10.3290/j.cjdr.a40437, PubMed:29808174
Histone Demethylase Jmjd7 Negatively Regulates Differentiation of Osteoclast
Liu, Yingci / Arai, Atsushi / Kim, Terresa / Kim, Sol / Park, No-hee / Kim, Reuben H.
Objective: To identify and verify the histone modifier during osteoclastogenesis.
Methods: Murine macrophage-like cell line, RAW 264.7 cells, or murine bone marrow macrophages (BMMs) were treated with a receptor activator of nuclear factor B ligand (RANKL) alone or RANKL with macrophage colony-stimulating factor (M-CSF), respectively, to induce differentiation of osteoclast. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen different arrays of histone demethylases. Chromatin immunoprecipitation (ChIP) assay was used to examine occupancy of jumonji domain containing 7 (Jmjd7) in the promoter regions of different osteoclast-related genes. Jmjd7 was knocked down using siRNA. Dentine slice assay was used to evaluate bone-resorptive functions.
Results: Among the screened histone demethylases, Jmjd7 was significantly downregulated during differentiation of osteoclast. The occupancy of Jmjd7 at the promoter regions of osteoclast-related genes was also decreased. Knockdown of Jmjd7 in RAW 264.7 cells and BMMs enhanced differentiation of osteoclast and increased the expression of osteoclast-related genes, such as c-fos, Dc-stamp, CtsK, Acp5, and Nfatc1. Bone resorptive functions of the cells were also increased.
Conclusion: Our study shows that Jmjd7, a histone demethylase, functions as a negative regulator of osteoclastogenesis, and may be a therapeutic target of bone-related diseases.
Keywords: Jmjd7, differentiation of osteoclast, RANKL, histone demethylases