The simultaneous inhibitory effect of niclosamide on RANKL-induced osteoclast formation and osteoblast differentiation

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

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7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)840-852
Number of pages13
JournalInternational Journal of Medical Sciences
Volume14
Issue number9
DOIs
Publication statusPublished - 2017

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Keywords

  • Niclosamide
  • Osteoblast differentiation
  • Osteoclast formation

ASJC Scopus subject areas

  • Medicine(all)

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