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

Bitnara Lee, Younseo Oh, Sungsin Jo, Tae Hwan Kim, Jong Dae Ji

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    26 Citations (Scopus)


    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 languageEnglish
    Pages (from-to)33-40
    Number of pages8
    JournalImmunology Letters
    Publication statusPublished - 2019 Feb

    Bibliographical note

    Funding Information:
    This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2017R 1D 1A 1B03028389 to Jong Dae Ji) and the Ministry of Science, ICT, & Future ( NRF-2016R1A2B4008606 ), and a grant of the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea ( HI17C0888 ).

    Publisher Copyright:
    © 2018 European Federation of Immunological Societies


    • Osteoclast
    • Smad1
    • Smad3
    • TGF-β

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology


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