Benzydamine inhibits osteoclast differentiation and bone resorption via down-regulation of interleukin-1β expression

• Published in: Acta pharmaceutica Sinica. B 2020-03, Vol.10 (3), p.462-474
• Main Authors: Son, Han Saem, Lee, Jiae, Lee, Hye In, Kim, Narae, Jo, You-Jin, Lee, Gong-Rak, Hong, Seong-Eun, Kwon, Minjeong, Kim, Nam Young, Kim, Hyun Jin, Park, Jin Ha, Lee, Soo Young, Jeong, Woojin
• Format: Article
• Language: English
• Subjects: Activator protein-1; Benzydamine; Bone; Interleukin-1β; Nuclear factor-κB; Original article; Osteoclast
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2019.11.004

Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity, which is closely associated with inflammation. Benzydamine (BA) has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of pro-inflammatory cytokines or prostaglandins. However, its role in osteoclast differentiation and function remains unknown. Here, we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism. BA inhibited osteoclast differentiation and strongly suppressed interleukin-1β (IL-1β) production. BA inhibited osteoclast formation and bone resorption when added to bone marrow-derived macrophages and differentiated osteoclasts, and the inhibitory effect was reversed by IL-1β treatment. The reporter assay and the inhibitor study of IL-1β transcription suggested that BA inhibited nuclear factor-κB and activator protein-1 by regulating IκB kinase, extracellular signal regulated kinase and P38, resulting in the down-regulation of IL-1β expression. BA also promoted osteoblast differentiation. Furthermore, BA protected lipopolysaccharide- and ovariectomy-induced bone loss in mice, suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis. The role of BA was explored in regulating osteoclast differentiation and the underlying mechanism was elucidated. BA inhibits osteoclast differentiation and resorption by suppressing IL-1β synthesis via down-regulation of IKK, ERK and P38, and promotes osteoblast differentiation. [Display omitted]