Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss

The activity of protein kinases IKK-ε and TANK-binding kinase 1 (TBK1) has been shown to be associated with inflammatory diseases. As an inhibitor of IKK-ε and TBK1, amlexanox is an anti-inflammatory, anti-allergic, immunomodulator and used for treatment of ulcer, allergic rhinitis and asthma in cli...

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Main Authors:	Zhang, Yong, Guan, Hanfeng, Li, Jing, Fang, Zhong, Chen, Wenjian, Li, Feng
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559750/

id	pubmed-4559750
recordtype	oai_dc
spelling	pubmed-45597502015-09-11 Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss Zhang, Yong Guan, Hanfeng Li, Jing Fang, Zhong Chen, Wenjian Li, Feng Article The activity of protein kinases IKK-ε and TANK-binding kinase 1 (TBK1) has been shown to be associated with inflammatory diseases. As an inhibitor of IKK-ε and TBK1, amlexanox is an anti-inflammatory, anti-allergic, immunomodulator and used for treatment of ulcer, allergic rhinitis and asthma in clinic. We hypothesized that amlexanox may be used for treatment of osteoclast-related diseases which frequently associated with a low grade of systemic inflammation. In this study, we investigated the effects of amlexanox on RANKL-induced osteoclastogenesis in vitro and ovariectomy-mediated bone loss in vivo. In primary bone marrow derived macrophages (BMMs), amlexanox inhibited osteoclast formation and bone resorption. At the molecular level, amlexanox suppressed RANKL-induced activation of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPKs), c-Fos and NFATc1. Amlexanox decreased the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. Moreover, amlexanox enhanced osteoblast differentiation of BMSCs. In ovariectomized (OVX) mouse model, amlexanox prevented OVX-induced bone loss by suppressing osteoclast activity. Taken together, our results demonstrate that amlexanox suppresses osteoclastogenesis and prevents OVX-induced bone loss. Therefore, amlexanox may be considered as a new therapeutic candidate for osteoclast-related diseases, such as osteoporosis and rheumatoid arthritis. Nature Publishing Group 2015-09-04 /pmc/articles/PMC4559750/ /pubmed/26338477 http://dx.doi.org/10.1038/srep13575 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhang, Yong Guan, Hanfeng Li, Jing Fang, Zhong Chen, Wenjian Li, Feng
spellingShingle	Zhang, Yong Guan, Hanfeng Li, Jing Fang, Zhong Chen, Wenjian Li, Feng Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss
author_facet	Zhang, Yong Guan, Hanfeng Li, Jing Fang, Zhong Chen, Wenjian Li, Feng
author_sort	Zhang, Yong
title	Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss
title_short	Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss
title_full	Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss
title_fullStr	Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss
title_full_unstemmed	Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss
title_sort	amlexanox suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss
description	The activity of protein kinases IKK-ε and TANK-binding kinase 1 (TBK1) has been shown to be associated with inflammatory diseases. As an inhibitor of IKK-ε and TBK1, amlexanox is an anti-inflammatory, anti-allergic, immunomodulator and used for treatment of ulcer, allergic rhinitis and asthma in clinic. We hypothesized that amlexanox may be used for treatment of osteoclast-related diseases which frequently associated with a low grade of systemic inflammation. In this study, we investigated the effects of amlexanox on RANKL-induced osteoclastogenesis in vitro and ovariectomy-mediated bone loss in vivo. In primary bone marrow derived macrophages (BMMs), amlexanox inhibited osteoclast formation and bone resorption. At the molecular level, amlexanox suppressed RANKL-induced activation of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPKs), c-Fos and NFATc1. Amlexanox decreased the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. Moreover, amlexanox enhanced osteoblast differentiation of BMSCs. In ovariectomized (OVX) mouse model, amlexanox prevented OVX-induced bone loss by suppressing osteoclast activity. Taken together, our results demonstrate that amlexanox suppresses osteoclastogenesis and prevents OVX-induced bone loss. Therefore, amlexanox may be considered as a new therapeutic candidate for osteoclast-related diseases, such as osteoporosis and rheumatoid arthritis.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559750/
_version_	1613472723662536704

Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss

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