A dual role of TGF-β in human osteoclast differentiation mediated by Smad1 versus Smad3 signaling
- Authors
- Lee, Bitnara; Oh, Younseo; Jo, Sungsin; Kim, Tae-Hwan; Ji, Jong Dae
- Issue Date
- Feb-2019
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Osteoclast; TGF-beta; Smad1; Smad3
- Citation
- IMMUNOLOGY LETTERS, v.206, pp.33 - 40
- Indexed
- SCIE
SCOPUS
- Journal Title
- IMMUNOLOGY LETTERS
- Volume
- 206
- Start Page
- 33
- End Page
- 40
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/15068
- DOI
- 10.1016/j.imlet.2018.12.003
- ISSN
- 0165-2478
- 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.
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