摘要
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 proinflammatory 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 marrowderived macrophages and differentiated osteoclasts,and the inhibitory effect was reversed by IL-1βtreatment.The reporter assay and the inhibitor study of IL-1βtranscription 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-1βexpression.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.
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 proinflammatory 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 marrowderived 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.
基金
supported by the National Research Foundation(NRF)(Grant Nos.2017R1A2B2012435,2019R1C1C1011198 and 2019R1A5A6099645,Korea)
funded by the Korean Ministry of Science,ICT and future Planning(MSIP).
作者简介
Han Saem Son,These authors made equal contributions to this work;Jiae Lee,These authors made equal contributions to this work;Corresponding author:Woojin Jeong,Tel.:+82232774495,fax:+82232773760,E-mail address:jeongw@ewha.ac.kr
