Bropirimine inhibits osteoclast differentiation through production of interferon-β

Journal Article · Fri Nov 06 00:00:00 EST 2015 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2015.09.092· OSTI ID:22592791

Suzuki, Hiroaki ^[1]; Mochizuki, Ayako ^[2]; Yoshimura, Kentaro; Miyamoto, Yoichi ^[1]; Kaneko, Kotaro ^[1]; Inoue, Tomio ^[2]; Chikazu, Daichi ^[3]; Takami, Masamichi ^[4]; Kamijo, Ryutaro ^[1]

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1. Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555 (Japan)
2. Department of Oral Physiology, Showa University School of Dentistry, Tokyo 142-8555 (Japan)
3. Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo 160-0023 (Japan)
4. Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555 (Japan)

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 D{sub 3}. Bropirimine partially suppressed the expression of RANKL mRNA in UAMS-32 cells induced by activated vitamin D{sub 3}. 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.

• OSTI ID: 22592791
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 467, Issue 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
BONE MARROW
BONE MARROW CELLS
CONCENTRATION RATIO
IN VITRO
INTERFERON
LIGANDS
MACROPHAGES
MESSENGER-RNA
MICE
RECEPTORS
SKELETON
TRANSCRIPTION
TRANSCRIPTION FACTORS
VITAMIN D