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

Research output: Contribution to journalArticle

70 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

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Osteoclasts
Osteogenesis
Interferons
Cytokines
Ligands
Interferon Type I
Interferon-Stimulated Gene Factor 3
Bone
Bone Resorption
Bone and Bones
Phosphorylation
Macrophage Colony-Stimulating Factor
Macrophages
Immune system
Gene Expression Regulation
Response Elements
Transforming Growth Factors
Neutralizing Antibodies
Gene expression
Immune System

ASJC Scopus subject areas

  • Biochemistry

Cite this

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. / Hayashi, Toshikichi; Kaneda, Toshio; Toyama, Yoshiaki; Kumegawa, Masayoshi; Hakeda, Yoshiyuki.

In: Journal of Biological Chemistry, Vol. 277, No. 31, 02.08.2002, p. 27880-27886.

Research output: Contribution to journalArticle

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