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Osteoporosis International

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01-08-2013 | Original Article

Dextromethorphan inhibits osteoclast differentiation by suppressing RANKL-induced nuclear factor-κB activation

Authors: Karl Wu, Tzu-Hung Lin, Houng-Chi Liou, Dai-Hua Lu, Yi-Ru Chen, Wen-Mei Fu, Rong-Sen Yang

Published in: Osteoporosis International | Issue 8/2013

Abstract

Summary

Dextromethorphan (DXM), a commonly used antitussive, is a dextrorotatory morphinan. Here, we report that DXM inhibits the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption by abrogating the activation of NF-κB signalling in vitro. Oral administration of DXM ameliorates ovariectomy (OVX)-induced osteoporosis in vivo.

Introduction

DXM was reported to possess anti-inflammatory properties through inhibition of the release of pro-inflammatory factors. However, the potential role and action mechanism of DXM on osteoclasts and osteoblasts remain unclear. In this study, in vitro and in vivo studies were performed to investigate the potential effects of DXM on osteoclastogenesis and OVX-induced bone loss.

Methods

Osteoclastogenesis was examined by the TRAP staining, pit resorption, TNF-α release, and CCR2 and CALCR gene expression. Osteoblast differentiation was analyzed by calcium deposition. Osteogenic and adipogenic genes were measured by real-time PCR. Signaling pathways were explored using Western blot. ICR mice were used in an OVX-induced osteoporosis model. Tibiae were measured by µCT and serum markers were examined with ELISA kits.

Results

DXM inhibited RANKL-induced osteoclastogenesis. DXM mainly inhibited osteoclastogenesis via abrogation of IKK-IκBα-NF-κB pathways. However, a higher dosage of DXM antagonized the differentiation of osteoblasts via the inhibition of osteogenic signals and increase of adipogenic signals. Oral administration of DXM (20 mg/kg/day) partially reduced trabecular bone loss in ovariectomized mice.

Conclusion

DXM inhibits osteoclast differentiation and activity by affecting NF-κB signaling. Therefore, DXM at suitable doses may have new therapeutic applications for the treatment of diseases associated with excessive osteoclastic activity.

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Title: Dextromethorphan inhibits osteoclast differentiation by suppressing RANKL-induced nuclear factor-κB activation
Authors: Karl Wu
Tzu-Hung Lin
Houng-Chi Liou
Dai-Hua Lu
Yi-Ru Chen
Wen-Mei Fu
Rong-Sen Yang
Publication date: 01-08-2013
Publisher: Springer London
Published in: Osteoporosis International / Issue 8/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-013-2279-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Dextromethorphan inhibits osteoclast differentiation by suppressing RANKL-induced nuclear factor-κB activation

Abstract

Summary

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

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