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

Title
A dual role of TGF-β in human osteoclast differentiation mediated by Smad1 versus Smad3 signaling.
Author
조성신
Keywords
Osteoclast; TGF-beta; Smad1; Smad3
Issue Date
2018-12
Publisher
ELSEVIER SCIENCE BV
Citation
IMMUNOLOGY LETTERS, v. 206, page. 33-40
Abstract
TGF-beta 1 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-beta 1 is still unclear in osteoclastogenesis. In this study, we examined the effect of TGF-beta 11 on osteoclast differentiation and the underlying mechanism using healthy human peripheral blood monocytes. TGF-beta 1 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-beta 11 suppressed receptor activator of NF-x13 (RANK) ligand-induced NF-kappa B and p38 MAPK signaling. Inhibition of osteoclast differentiation by TGF-beta 1 was reversed by 1 pM SB431542 (an inhibitor of ALK4/5/7), which inhibited TGF-beta 1-induced phosphorylation of SMAD1, but not that of SMAD3. TGF-beta 1 also restricted RANK expression, and this was partially reversed by 1 pM SB431542. In contrast, the inhibition of SMAD3 by SIS3 (an inhibitor of SMAD3) reduced the osteoclast formation. TGF-f31 has both inhibitory and stimulatory effects on human osteoclast differentiation, and that these opposing functions are mediated by SMAD1 and SMAD3 signaling, respectively.
URI
https://www.sciencedirect.com/science/article/abs/pii/S0165247818304206?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/121039
ISSN
0165-2478; 1879-0542
DOI
10.1016/j.imlet.2018.12.003
Appears in Collections:
RESEARCH INSTITUTE[S](부설연구소) > ETC
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