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Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss.
Sci Rep. 2015 Sep 04; 5:13575.SR

Abstract

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.

Authors+Show Affiliations

From the Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, P.R.China.From the Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, P.R.China.From the Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, P.R.China.From the Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, P.R.China.From the Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, P.R.China.From the Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, P.R.China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26338477

Citation

Zhang, Yong, et al. "Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss." Scientific Reports, vol. 5, 2015, p. 13575.
Zhang Y, Guan H, Li J, et al. Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss. Sci Rep. 2015;5:13575.
Zhang, Y., Guan, H., Li, J., Fang, Z., Chen, W., & Li, F. (2015). Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss. Scientific Reports, 5, 13575. https://doi.org/10.1038/srep13575
Zhang Y, et al. Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss. Sci Rep. 2015 Sep 4;5:13575. PubMed PMID: 26338477.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss. AU - Zhang,Yong, AU - Guan,Hanfeng, AU - Li,Jing, AU - Fang,Zhong, AU - Chen,Wenjian, AU - Li,Feng, Y1 - 2015/09/04/ PY - 2015/01/11/received PY - 2015/07/31/accepted PY - 2015/9/5/entrez PY - 2015/9/5/pubmed PY - 2016/7/28/medline SP - 13575 EP - 13575 JF - Scientific reports JO - Sci Rep VL - 5 N2 - 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. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/26338477/Amlexanox_Suppresses_Osteoclastogenesis_and_Prevents_Ovariectomy_Induced_Bone_Loss_ L2 - http://dx.doi.org/10.1038/srep13575 DB - PRIME DP - Unbound Medicine ER -