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.
Original language | English |
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Pages (from-to) | 33-40 |
Number of pages | 8 |
Journal | Immunology Letters |
Volume | 206 |
DOIs | |
Publication status | Published - 2019 Feb |
Keywords
- Osteoclast
- Smad1
- Smad3
- TGF-β
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology