title: Bropirimine inhibits osteoclast differentiation through production of interferon-β.
abstract: Bropirimine is a synthetic agonist for toll-like receptor 7 (TLR7). In this study, we investigated the effects of bropirimine on differentiation and bone-resorbing activity of osteoclasts in vitro. Bropirimine inhibited osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) induced by receptor activator of nuclear factor κB ligand (RANKL) in a concentration-dependent manner. Furthermore, it suppressed the mRNA expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), a master transcription factor for osteoclast differentiation, without affecting BMM viability. Bropirimine also inhibited osteoclast differentiation induced in co-cultures of mouse bone marrow cells (BMCs) and mouse osteoblastic UAMS-32 cells in the presence of activated vitamin D3. Bropirimine partially suppressed the expression of RANKL mRNA in UAMS-32 cells induced by activated vitamin D3. Finally, the anti-interferon-β (IFN-β) antibody restored RANKL-dependent differentiation of BMMs into osteoclasts suppressed by bropirimine. These results suggest that bropirimine inhibits differentiation of osteoclast precursor cells into osteoclasts via TLR7-mediated production of IFN-β.
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Oral Physiology, Showa University School of Dentistry, Tokyo 142-8555, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Mochizuki
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan; Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Oral Physiology, Showa University School of Dentistry, Tokyo 142-8555, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Chikazu
authors.affiliation: Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Takami
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan. Electronic address: kamijor@dent.showa-u.ac.jp.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kamijo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016899:Interferon-beta / Q000096:biosynthesis*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000819:agonists; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000819:agonists
chemical_list: D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; C477038:Tlr7 protein, mouse; C505689:Tnfsf11 protein, mouse; D051199:Toll-Like Receptor 7; D016899:Interferon-beta; D003596:Cytosine; C033560:bropirimine
keywords: Differentiation; Interferon-β; Osteoclasts; Toll-like receptor-7