PMID- 26399683 OWN - NLM STAT- MEDLINE DCOM- 20160408 LR - 20151016 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 467 IP - 1 DP - 2015 Nov 6 TI - Bropirimine inhibits osteoclast differentiation through production of interferon-beta. PG - 146-51 LID - S0006-291X(15)30609-4 [pii] LID - 10.1016/j.bbrc.2015.09.092 [doi] AB - 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 kappaB 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-beta (IFN-beta) 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-beta. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Suzuki, Hiroaki AU - Suzuki H AD - Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan. FAU - Mochizuki, Ayako AU - Mochizuki A AD - Department of Oral Physiology, Showa University School of Dentistry, Tokyo 142-8555, Japan. FAU - Yoshimura, Kentaro AU - Yoshimura K AD - Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan. FAU - Miyamoto, Yoichi AU - Miyamoto Y AD - Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan. FAU - Kaneko, Kotaro AU - Kaneko K AD - 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. FAU - Inoue, Tomio AU - Inoue T AD - Department of Oral Physiology, Showa University School of Dentistry, Tokyo 142-8555, Japan. FAU - Chikazu, Daichi AU - Chikazu D AD - Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo 160-0023, Japan. FAU - Takami, Masamichi AU - Takami M AD - Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555, Japan. FAU - Kamijo, Ryutaro AU - Kamijo R AD - Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan. Electronic address: kamijor@dent.showa-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150921 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Membrane Glycoproteins) RN - 0 (RANK Ligand) RN - 0 (RNA, Messenger) RN - 0 (Tlr7 protein, mouse) RN - 0 (Tnfsf11 protein, mouse) RN - 0 (Toll-Like Receptor 7) RN - 77238-31-4 (Interferon-beta) RN - 8J337D1HZY (Cytosine) RN - J57CTF25XJ (bropirimine) SB - IM MH - Animals MH - Cell Differentiation/drug effects/immunology MH - Cell Line MH - Coculture Techniques MH - Cytosine/*analogs & derivatives/pharmacology MH - Interferon-beta/*biosynthesis MH - Macrophages/cytology/drug effects/immunology MH - Male MH - Membrane Glycoproteins/agonists MH - Mice MH - Mice, Inbred C57BL MH - Osteoclasts/*cytology/*drug effects/immunology MH - RANK Ligand/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - Toll-Like Receptor 7/agonists OTO - NOTNLM OT - Differentiation OT - Interferon-beta OT - Osteoclasts OT - Toll-like receptor-7 EDAT- 2015/09/25 06:00 MHDA- 2016/04/09 06:00 CRDT- 2015/09/25 06:00 PHST- 2015/09/02 00:00 [received] PHST- 2015/09/17 00:00 [accepted] PHST- 2015/09/25 06:00 [entrez] PHST- 2015/09/25 06:00 [pubmed] PHST- 2016/04/09 06:00 [medline] AID - S0006-291X(15)30609-4 [pii] AID - 10.1016/j.bbrc.2015.09.092 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2015 Nov 6;467(1):146-51. doi: 10.1016/j.bbrc.2015.09.092. Epub 2015 Sep 21.