Activation of NF-kappaB is involved in the survival of osteoclasts promoted by interleukin-1

J Biol Chem. 1998 Apr 10;273(15):8799-805. doi: 10.1074/jbc.273.15.8799.

Abstract

We previously reported that interleukin-1 (IL-1) promoted the survival of murine osteoclast-like cells (OCLs) formed in vitro and activated a transcription factor, NF-kappaB, of OCLs. The present study examined whether the activation of NF-kappaB is directly involved in the survival of OCLs promoted by IL-1. The expression of IL-1 type I receptor mRNA in OCLs was detected by the polymerase chain reaction amplification of reverse-transcribed mRNA. An electrophoretic mobility shift assay showed that IL-1 transiently activated NF-kappaB in the nuclei of the OCLs, and the maximal activation occurred at 30 min. The degradation of IkappaBalpha coincided with the activation of NF-kappaB in the OCLs. The immunocytochemical study revealed that p65, a subunit of NF-kappaB, was translocated from the cytoplasm into almost all of the nuclei of the OCLs within 30 min after IL-1 stimulation. The purified OCLs spontaneously died via apoptosis, and IL-1 promoted the survival of OCLs by preventing their apoptosis. The pretreatment of purified OCLs with proteasome inhibitors suppressed the IL-1-induced activation of NF-kappaB and prevented the survival of OCLs supported by IL-1. When OCLs were pretreated with antisense oligodeoxynucleotides to p65 and p50 of NF-kappaB, the expression of respective mRNAs by OCLs was suppressed, and the IL-1-induced survival of OCLs was concomitantly inhibited. These results indicate that IL-1 promotes the survival of osteoclasts through the activation of NF-kappaB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Bone Marrow Cells / cytology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology
  • DNA Primers
  • Dactinomycin / pharmacology
  • Interleukin-1 / pharmacology*
  • Mice
  • Multienzyme Complexes / metabolism
  • NF-kappa B / biosynthesis*
  • Oligodeoxyribonucleotides
  • Oligonucleotides, Antisense
  • Osteoblasts / cytology
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Polymerase Chain Reaction
  • Proteasome Endopeptidase Complex
  • RNA, Messenger / biosynthesis
  • Receptors, Interleukin-1 / biosynthesis*
  • Thionucleotides
  • Transcription, Genetic / drug effects

Substances

  • Cysteine Proteinase Inhibitors
  • DNA Primers
  • Interleukin-1
  • Multienzyme Complexes
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Thionucleotides
  • Dactinomycin
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex