2. Academic Validation
  3. Bropirimine inhibits osteoclast differentiation through production of interferon-β

Bropirimine inhibits osteoclast differentiation through production of interferon-β

  • Biochem Biophys Res Commun. 2015 Nov 6;467(1):146-51. doi: 10.1016/j.bbrc.2015.09.092.
Hiroaki Suzuki 1,  Ayako Mochizuki 2,  Kentaro Yoshimura 1,  Yoichi Miyamoto 1,  Kotaro Kaneko 3,  Tomio Inoue 2,  Daichi Chikazu 4,  Masamichi Takami 5,  Ryutaro Kamijo 6
Affiliations

Affiliations

  • 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 Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan; Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
  • 4 Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
  • 5 Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555, Japan.
  • 6 Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan. Electronic address: [email protected].
PMID: 26399683 DOI: 10.1016/j.bbrc.2015.09.092
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.

Keywords

Differentiation; Interferon-β; Osteoclasts; Toll-like receptor-7.

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