TRAF-6 dependent signaling pathway is essential for TNF-related apoptosis-inducing ligand (TRAIL) induces Osteoclast differentiation

Men Luh Yen, Ping Ning Hsu, Hsiu Jung Liao, Be Hang Lee, Huei-Fang Tsai

Research output: Contribution to journalArticle

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Abstract

Human osteoclast formation from mononuclear phagocyte precursors involves interactions between tumor necrosis factor (TNF) ligand superfamily members and their receptors. Recent evidence indicates that in addition to triggering apoptosis, the TNF-related apoptosis-inducing ligand (TRAIL) induces osteoclast differentiation. To understand TRAIL-mediated signal transduction mechanism in osteoclastogenesis, we demonstrated that TRAIL induces osteoclast differentiation via a Tumor necrosis factor receptor-associated factor 6 (TRAF-6)-dependent signaling pathway. TRAIL-induced osteoclast differentiation was significantly inhibited by treatment with TRAF-6 siRNA and TRAF6 decoy peptides in both human monocytes and murine RAW264.7 macrophage cell lines, as evaluated in terms of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and bone resorption activity. Moreover, TRAIL-induced osteoclast differentiation was also abolished in TRAF6 knockout bone marrow macrophages. In addition to induction of NFATc1, treatment of TRAIL also induced ubiquitination of TRAF6 in osteoclast differentiation. Thus, our data demonstrate that TRAIL induces osteoclastic differentiation via a TRAF-6 dependent signaling pathway. This study suggests TRAF6-dependent signaling may be a central pathway in osteoclast differentiation, and that TNF superfamily molecules other than RANKL may modify RANK signaling by interaction with TRAF6-associated signaling.

Original languageEnglish
Article numbere38048
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 14 2012

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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
TNF-Related Apoptosis-Inducing Ligand
osteoclasts
tumor necrosis factors
TNF Receptor-Associated Factor 6
Osteoclasts
apoptosis
Tumor Necrosis Factor-alpha
Apoptosis
Ligands
receptors
Macrophages
Bone
Tumor Necrosis Factors
macrophages
Signal transduction
Ubiquitination
Phagocytes
bone resorption
Bone Resorption

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

TRAF-6 dependent signaling pathway is essential for TNF-related apoptosis-inducing ligand (TRAIL) induces Osteoclast differentiation. / Yen, Men Luh; Hsu, Ping Ning; Liao, Hsiu Jung; Lee, Be Hang; Tsai, Huei-Fang.

In: PLoS One, Vol. 7, No. 6, e38048, 14.06.2012.

Research output: Contribution to journalArticle

Yen, Men Luh ; Hsu, Ping Ning ; Liao, Hsiu Jung ; Lee, Be Hang ; Tsai, Huei-Fang. / TRAF-6 dependent signaling pathway is essential for TNF-related apoptosis-inducing ligand (TRAIL) induces Osteoclast differentiation. In: PLoS One. 2012 ; Vol. 7, No. 6.
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