A dual role of TGF-β in human osteoclast differentiation mediated by Smad1 versus Smad3 signaling

Bitnara Lee, Younseo Oh, Sungsin Jo, Tae Hwan Kim, Jong Dae Ji

Research output: Contribution to journalArticle

Abstract

TGF-β1 is highly expressed in the synovial tissue of patients with rheumatoid arthritis and is known as a cytokine that plays an important role in tissue repair and immune cell regulation. However, the role of TGF-β1 is still unclear in osteoclastogenesis. In this study, we examined the effect of TGF-β1 on osteoclast differentiation and the underlying mechanism using healthy human peripheral blood monocytes. TGF-β1 was found to inhibit osteoclast differentiation and decrease the expression of osteoclast-specific genes such as acid phosphatase 5, tartrate resistant and cathepsin K. Levels of NFAT1, an important transcription factor in osteoclastogenesis, were also reduced. In addition, TGF-β1 suppressed receptor activator of NF-κB (RANK) ligand-induced NF-κB and p38 MAPK signaling. Inhibition of osteoclast differentiation by TGF-β1 was reversed by 1 μM SB431542 (an inhibitor of ALK4/5/7), which inhibited TGF-β1-induced phosphorylation of SMAD1, but not that of SMAD3. TGF-β1 also restricted RANK expression, and this was partially reversed by 1 μM SB431542. In contrast, the inhibition of SMAD3 by SIS3 (an inhibitor of SMAD3) reduced the osteoclast formation. TGF-β1 has both inhibitory and stimulatory effects on human osteoclast differentiation, and that these opposing functions are mediated by SMAD1 and SMAD3 signaling, respectively.

LanguageEnglish
Pages33-40
Number of pages8
JournalImmunology Letters
Volume206
DOIs
Publication statusPublished - 2019 Feb 1

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Osteoclasts
Transforming Growth Factor beta
Osteogenesis
Cathepsin K
RANK Ligand
p38 Mitogen-Activated Protein Kinases
Monocytes
Rheumatoid Arthritis
Transcription Factors
Phosphorylation
Cytokines
Genes

Keywords

  • Osteoclast
  • Smad1
  • Smad3
  • TGF-β

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

A dual role of TGF-β in human osteoclast differentiation mediated by Smad1 versus Smad3 signaling. / Lee, Bitnara; Oh, Younseo; Jo, Sungsin; Kim, Tae Hwan; Ji, Jong Dae.

In: Immunology Letters, Vol. 206, 01.02.2019, p. 33-40.

Research output: Contribution to journalArticle

Lee, Bitnara ; Oh, Younseo ; Jo, Sungsin ; Kim, Tae Hwan ; Ji, Jong Dae. / A dual role of TGF-β in human osteoclast differentiation mediated by Smad1 versus Smad3 signaling. In: Immunology Letters. 2019 ; Vol. 206. pp. 33-40.
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