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 |
|---|---|
| Pages (from-to) | 33-40 |
| Number of pages | 8 |
| Journal | Immunology Letters |
| Volume | 206 |
| DOIs | |
| Publication status | Published - 2019 Feb 1 |
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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 journal › Article
}
TY - JOUR
T1 - A dual role of TGF-β in human osteoclast differentiation mediated by Smad1 versus Smad3 signaling
AU - Lee, Bitnara
AU - Oh, Younseo
AU - Jo, Sungsin
AU - Kim, Tae Hwan
AU - Ji, Jong Dae
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - Osteoclast
KW - Smad1
KW - Smad3
KW - TGF-β
UR - http://www.scopus.com/inward/record.url?scp=85058409987&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058409987&partnerID=8YFLogxK
U2 - 10.1016/j.imlet.2018.12.003
DO - 10.1016/j.imlet.2018.12.003
M3 - Article
C2 - 30543834
AN - SCOPUS:85058409987
VL - 206
SP - 33
EP - 40
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
ER -