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

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

  • Immunol Lett. 2019 Feb;206:33-40. doi: 10.1016/j.imlet.2018.12.003.
Bitnara Lee 1,  Younseo Oh 2,  Sungsin Jo 3,  Tae-Hwan Kim 4,  Jong Dae Ji 5
Affiliations

Affiliations

  • 1 Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea; Research Institute of Molecular Medicine and Nutrition, Korea University, Seoul, South Korea.
  • 2 Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea; Rheumatology, College of Medicine, Korea University, Seoul, South Korea.
  • 3 Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
  • 4 Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea. Electronic address: [email protected].
  • 5 Rheumatology, College of Medicine, Korea University, Seoul, South Korea. Electronic address: [email protected].
PMID: 30543834 DOI: 10.1016/j.imlet.2018.12.003
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.

Keywords

Osteoclast; Smad1; Smad3; TGF-β.

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