Involvement of iNOS-dependent NO production in the stimulation of osteoclast survival by TNF-α

Seung Ku Lee, Hao Huang, Soo Woong Lee, Kyung Hee Kim, Kyung Keun Kim, Hyun Man Kim, Zang Hee Lee, Hong Hee Kim*

*Corresponding author for this work

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Osteoclasts, cells primarily responsible for bone resorption, differentiate from hematopoietic progenitor cells under the influence of various hormones, cytokines, and differentiation factors. Once fully differentiated, osteoclasts rapidly die in the absence of any survival factor. We have previously shown that tumor necrosis factor α (TNF-α) promotes the survival of differentiated osteoclasts. The expression of inducible nitric oxide synthase (iNOS) and consequent NO production is often stimulated under inflammatory conditions. In this study, we found that TNF-α, but not receptor activator of nuclear factor kappa B ligand and interleukin 1, increased the expression of iNOS both at the mRNA and protein levels. Subsequently, an enhanced NO level was detected both inside the cells and the culture medium of TNF-α-stimulated osteoclasts. Blocking NOS activity with L-NAME prevented TNF-α-induced NO generation by osteoclasts and the osteoclast survival stimulated by TNF-α. The iNOS selective inhibitor L-NIL also suppressed TNF-α-induced osteoclast survival, whereas low concentrations of NO releaser NOC-18 were sufficient to promote osteoclast survival. Furthermore, antiapoptotic and caspase suppressive effects of TNF-α on osteoclasts were abolished by L-NAME. Our findings indicate that iNOS-dependent NO generation contributes to the survival-promoting function of TNF-α in osteoclasts.

Original languageEnglish (US)
Pages (from-to)359-368
Number of pages10
JournalExperimental Cell Research
Volume298
Issue number2
DOIs
StatePublished - Aug 15 2004

Keywords

  • Apoptosis
  • Nitric oxide
  • Osteoclast
  • TNF-α
  • iNOS

ASJC Scopus subject areas

  • Cell Biology

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