title: BIX01294 suppresses osteoclast differentiation on mouse macrophage-like Raw264.7 cells.
abstract: Gene expressionis controlled by epigenetic mechanisms including histone methylation. Osteoclasts are bone-resorptive cells that differentiate from hematopoietic-precursor cells by receptor activator of nuclear factor-κB ligand (RANKL) stimulation. Although BIX01294, a specific inhibitor of G9a, which works as a histone H3 lysine 9 (H3K9) methyltransferase, reportedly changes cellular differentiational stage, its effect on osteoclast differentiation is unclear. In this study, the effects of BIX01294 on osteoclast differentiation were examined. Here, we showed that BIX01294 dose-dependently reduced RANKL-induced tartrate-resistant acid phosphatase positive multinuclear osteoclast-like cell differentiation from murine macrophage-like Raw264.7 cells. During differentiation, growth rates reduced only less than 14% of those of cells stimulated with RANKL alone by BIX01294 treatment. Moreover, western blot analysis showed that BIX01294 reduced RANKL-induced carbonic anhydrase II and cathepsin K production and decreased RANKL-induced nuclear factor of activated T-cell c1, a master regulatory transcription factor, production during osteoclast differentiation. These results suggest that BIX01294 suppresses RANKL-induced osteoclast differentiation. This is the first report about the effect of BIX01294 on osteoclast differentiation.
authors.affiliation: Department of Biochemistry, School of Dentistry, Nihon University, 1-8-13 Kanda Surugadai Chiyoda-ku, Tokyo 101-8310, Japan. Division of Functional Morphology and Immunology, Dental Research Center, School of Dentistry, Nihon University 1-8-13 Kanda Surugadai Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tsuda
authors.forename: Ning
authors.initials: N
authors.lastname: Zhao
authors.forename: Kenichi
authors.initials: K
authors.lastname: Imai
authors.forename: Kuniyasu
authors.initials: K
authors.lastname: Ochiai
authors.forename: Pishan
authors.initials: P
authors.lastname: Yang
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors; D006657:Histones / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008745:Methylation; D051379:Mice; D050778:NFATC Transcription Factors / Q000096:biosynthesis; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism
chemical_list: D001381:Azepines; C518299:BIX 01294; D004791:Enzyme Inhibitors; D006657:Histones; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D011799:Quinazolines; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase