The Simultaneous Inhibitory Effect of Niclosamide on RANKL-Induced Osteoclast Formation and Osteoblast Differentiation

Liu, Fei-Lan; Chen, Chun-Liang; Lee, Chia-Chung; Wu, Cheng-Chi; Hsu, Teng-Hsu; Tsai, Chang-Youh; Huang, Hsu-Shan; Chang, Deh-Ming

doi:10.7150/ijms.19268

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Int J Med Sci 2017; 14(9):840-852. doi:10.7150/ijms.19268 This issue Cite

Research Paper

The Simultaneous Inhibitory Effect of Niclosamide on RANKL-Induced Osteoclast Formation and Osteoblast Differentiation

Fei-Lan Liu^1,2#, Chun-Liang Chen^3#, Chia-Chung Lee³, Cheng-Chi Wu^1,3, Teng-Hsu Hsu¹, Chang-Youh Tsai¹, Hsu-Shan Huang³, Deh-Ming Chang^1,2,3✉

1. Rheumatology/Immunology/Allergy, Taipei Veterans General Hospital, Taiwan, Republic of China
2. Graduate Institute of Medical Sciences, National Defense Medical Center, Taiwan, Republic of China
3. Graduate Institutes of Life Sciences, National Defense Medical Center, Taiwan, Republic of China
# Both authors contributed equally to this work.

Citation:

Liu FL, Chen CL, Lee CC, Wu CC, Hsu TH, Tsai CY, Huang HS, Chang DM. The Simultaneous Inhibitory Effect of Niclosamide on RANKL-Induced Osteoclast Formation and Osteoblast Differentiation. Int J Med Sci 2017; 14(9):840-852. doi:10.7150/ijms.19268. https://www.medsci.org/v14p0840.htm

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Abstract

The bone destruction disease including osteoporosis and rheumatoid arthritis are caused by the imbalance between osteoblastogenesis and osteoclastogenesis. Inhibition of the NF-κB pathway was responsible for decreased osteoclastogenesis. Recently many studies indicated that niclosamide, the FDA approved an antihelminth drug, inhibits prostate and breast cancer cells growth by targeting NF-κB signaling pathways. This study evaluated the effects of niclosamide on osteoclast and osteoblast differentiation and function in vitro.

In RANKL-induced murine osteoclast precursor cell RAW264.7 and M-CSF/RANKL-stimulated primary murine bone marrow-derived macrophages (BMM), niclosamide dose-dependently inhibited the formation of TRAP-positive multinucleated osteoclasts and resorption pits formation between 0.5uM and 1uM. In addition, niclosamide suppressed the expression of nuclear factor of activated T cells c1 (NFATc1) and osteoclast differentiated-related genes in M-CSF/ RANKL-stimulated BMM by interference with TRAF-6, Erk1/2, JNK and NF-κB activation pathways. However, the cytotoxic effects of niclosamide obviously appeared at the effective concentrations for inhibiting osteoclastogenesis (0.5-1uM) with increase of apoptosis through caspase-3 activation in osteoblast precursor cell line, MC3T3-E1. Niclosamide also inhibited ALP activity, bone mineralization and osteoblast differentiation-related genes expression in MC3T3-E1. Therefore, our findings suggest the new standpoint that niclosamide's effects on bones must be considered before applying it in any therapeutic treatment.

Keywords: Niclosamide, Osteoclast Formation, Osteoblast Differentiation

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APA

Liu, F.L., Chen, C.L., Lee, C.C., Wu, C.C., Hsu, T.H., Tsai, C.Y., Huang, H.S., Chang, D.M. (2017). The Simultaneous Inhibitory Effect of Niclosamide on RANKL-Induced Osteoclast Formation and Osteoblast Differentiation. International Journal of Medical Sciences, 14(9), 840-852. https://doi.org/10.7150/ijms.19268.

ACS

Liu, F.L.; Chen, C.L.; Lee, C.C.; Wu, C.C.; Hsu, T.H.; Tsai, C.Y.; Huang, H.S.; Chang, D.M. The Simultaneous Inhibitory Effect of Niclosamide on RANKL-Induced Osteoclast Formation and Osteoblast Differentiation. Int. J. Med. Sci. 2017, 14 (9), 840-852. DOI: 10.7150/ijms.19268.

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CSE

Liu FL, Chen CL, Lee CC, Wu CC, Hsu TH, Tsai CY, Huang HS, Chang DM. 2017. The Simultaneous Inhibitory Effect of Niclosamide on RANKL-Induced Osteoclast Formation and Osteoblast Differentiation. Int J Med Sci. 14(9):840-852.

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