Next Article in Journal
Halogen-Mediated Partial Oxidation of Polyvinyl Alcohol for Tissue Engineering Purposes
Next Article in Special Issue
At the Crossroads of the Adipocyte and Osteoclast Differentiation Programs: Future Therapeutic Perspectives
Previous Article in Journal
Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review
Previous Article in Special Issue
A Sub-Clone of RAW264.7-Cells Form Osteoclast-Like Cells Capable of Bone Resorption Faster than Parental RAW264.7 through Increased De Novo Expression and Nuclear Translocation of NFATc1
Article

TGFβ1 Regulates Human RANKL-Induced Osteoclastogenesis via Suppression of NFATc1 Expression

Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima 734-8551, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 800; https://doi.org/10.3390/ijms21030800
Received: 4 January 2020 / Revised: 21 January 2020 / Accepted: 23 January 2020 / Published: 25 January 2020
(This article belongs to the Special Issue Osteoclast Multinucleation Mechanisms)
Osteoclasts are multinucleated giant cells responsible for bone resorption. Various mediators involved in osteoclast differentiation have been investigated as possible therapeutic targets for osteoporosis and rheumatoid arthritis (RA). Although transforming growth factor beta1 (TGFβ1) has been described as one such multifunctional cytokine essential for bone remodeling, its effect on osteoclastogenesis remains controversial. Therefore, we sought to examine the effect of TGFβ1 on osteoclast generation induced by receptor activator of nuclear factor (NF)-κB ligand (RANKL) in humans. Peripheral blood monocytes, isolated using magnetic bead sorting, were cultured with macrophage-colony stimulating factor (M-CSF) or RANKL with or without TGFβ1. Tartrate-resistant acid phosphatase (TRAP) staining, as well as bone resorption assays, revealed that TGFβ1 suppressed RANKL-mediated human osteoclast development. Real-time reverse transcription PCR and Western blotting revealed that TGFβ1 reduced the gene and protein expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), the master regulator of osteoclast differentiation, respectively. Luciferase assays indicated that TGFβ1 inhibited the NF-κB p65-stimulated promoter activity of NFATc1. Immunofluorescence analysis demonstrated that TGFβ1 abrogated RANKL-induced nuclear translocation of p65. Thus, TGFβ1 regulates human RANKL-induced osteoclastogenesis via downregulation of NFATc1 by blocking nuclear translocation of NF-κB, suggesting that TGFβ1 may be a potential therapeutic target for RA. View Full-Text
Keywords: human osteoclastogenesis; TGFβ1; RANKL; NFATc1; NF-κB; rheumatoid arthritis human osteoclastogenesis; TGFβ1; RANKL; NFATc1; NF-κB; rheumatoid arthritis
Show Figures

Graphical abstract

MDPI and ACS Style

Tokunaga, T.; Mokuda, S.; Kohno, H.; Yukawa, K.; Kuranobu, T.; Oi, K.; Yoshida, Y.; Hirata, S.; Sugiyama, E. TGFβ1 Regulates Human RANKL-Induced Osteoclastogenesis via Suppression of NFATc1 Expression. Int. J. Mol. Sci. 2020, 21, 800. https://doi.org/10.3390/ijms21030800

AMA Style

Tokunaga T, Mokuda S, Kohno H, Yukawa K, Kuranobu T, Oi K, Yoshida Y, Hirata S, Sugiyama E. TGFβ1 Regulates Human RANKL-Induced Osteoclastogenesis via Suppression of NFATc1 Expression. International Journal of Molecular Sciences. 2020; 21(3):800. https://doi.org/10.3390/ijms21030800

Chicago/Turabian Style

Tokunaga, Tadahiro; Mokuda, Sho; Kohno, Hiroki; Yukawa, Kazutoshi; Kuranobu, Tatsuomi; Oi, Katsuhiro; Yoshida, Yusuke; Hirata, Shintaro; Sugiyama, Eiji. 2020. "TGFβ1 Regulates Human RANKL-Induced Osteoclastogenesis via Suppression of NFATc1 Expression" Int. J. Mol. Sci. 21, no. 3: 800. https://doi.org/10.3390/ijms21030800

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop