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

Han Saem Son, Jiae Lee, Hye In Lee, Narae Kim, You Jin Jo, Gong Rak Lee, Seong Eun Hong, Minjeong Kwon, Nam Young Kim, Hyun Jin Kim, Jin Ha Park, Soo Young Lee, Woojin Jeong

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)462-474
Number of pages13
JournalActa Pharmaceutica Sinica B
Volume10
Issue number3
DOIs
StatePublished - Mar 2020

Bibliographical note

Publisher Copyright:
© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences

Keywords

  • Activator protein-1
  • Benzydamine
  • Bone
  • Interleukin-1β
  • Nuclear factor-κB
  • Osteoclast

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