Regulation of receptor activator of NF-κB ligand-induced osteoclastogenesis by endogenous interferon-β (INF-β) and suppressors of cytokine signaling (SOCS). The possible counteracting role of SOCSs in IFN-β-inhibited osteoclast formation

Toshikichi Hayashi, Toshio Kaneda, Yoshiaki Toyama, Masayoshi Kumegawa, Yoshiyuki Hakeda

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71 Citations (Scopus)

Abstract

Bone resorption and the immune system are correlated with each other, and both are controlled by a variety of common cytokines produced in the bone microenvironments. Among these immune mediators, the involvement of type I interferons (IFNs) in osteoclastic bone resorption remains unknown. In this study, we investigated the participation of IFN-β and suppressors of cytokine signaling (SOCS)-1 and -3 in osteoclastogenesis. Addition of exogenous IFN-β to osteoclast progenitors (bone-derived monocytes/macrophages) inhibited their differentiation toward osteoclasts induced by the receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor with/without transforming growth factor-β, where inhibition was associated with down-regulation of the gene expressions of molecules related to osteoclast differentiation. In addition, RANKL induced the expression of IFN-β; furthermore, neutralizing antibody against type I IFNs accelerated the osteoclast formation, indicating type I IFNs as potential intrinsic inhibitors. On the other hand, RANKL also induced the expression of SOCS-1 and -3, suppressors of the IFN signaling. Pretreatment with RANKL for a sufficient time for the induction of SOCSs attenuated phosphorylation of STAT-1 in response to IFN-β in osteoclast progenitors, causing a decrease in the binding activity of nuclear extracts toward the interferon-stimulated response element. mRNA levels of STAT-1, STAT-2, and IFN-stimulated gene factor-3γ, comprising IFN-stimulated gene factor-3, were not altered by RANKL. Thus, although the inhibitory cytokine such as IFN-β is produced in response to RANKL, the inhibition of osteoclastogenesis may be rescued by the induction of signaling suppressors such as SOCSs.

Original languageEnglish
Pages (from-to)27880-27886
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number31
DOIs
Publication statusPublished - 2002 Aug 2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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