ABD56 causes osteoclast apoptosis by inhibiting the NFkappaB and ERK pathways

A. I. Idris, E. Mrak, Iain Robert Greig, R. J. van't Hof, S. H. Ralston

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Abstract

We have previously shown that the biphenylcarboxylic acid butanediol ester (ABD56) inhibits osteoclast formation and activity in vitro and in vivo. However, the mechanism of action of this compound is unknown. ABD56 inhibited osteoclast formation and caused osteoclast apoptosis, but had no effects on osteoblasts or macrophages. As the NF kappa B and MAPK pathways are essential for osteoclast formation and survival, we studied the effects of ABD56 on these pathways. ABD56 caused phosphorylation of p38, JNK and nuclear translocation of c-jun in osteoclasts. ABD56-induced apoptosis was prevented by the caspase inhibitor zVAD-fmk but was not prevented by the p38- or JNK-inhibitors. ABD56 completely abolished RANKL-induced I kappa B and ERK1/2 phosphorylation. Increasing the amount of RANKL partially rescued ABD56-induced apoptosis, indicating that the apoptosis is most probably due to the inhibition of survival signals such as ERK and NF kappa B, rather than activation of the p38 or Jnk MAPK pathways. (c) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)94-98
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume371
Issue number1
Early online date14 Apr 2008
DOIs
Publication statusPublished - 20 Jun 2008

Keywords

  • osteoclast
  • apoptosis
  • RANKL
  • NF kappa B
  • JNK
  • ERK
  • p38
  • activated protein-kinase
  • bone-resorption
  • in-vitro
  • receptor activator
  • map kinases
  • differentiation
  • induction
  • survival

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