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Updated: Mar 10, 2026

Differentiation and Characterization of Osteoclasts from Human Induced Pluripotent Stem Cells
Published on: March 22, 2024
Sulforaphane inhibits osteoclast differentiation by suppressing the cell-cell fusion molecules DC-STAMP and OC-STAMP
Tomohiro Takagi1, Hirofumi Inoue1, Nobuyuki Takahashi1
1Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
Abstract:
Sulforaphane (SFN), a kind of isothiocyanate, is derived from broccoli sprouts. It has anti-tumor, anti-inflammatory, and anti-oxidation activity. The molecular function of SFN in the inhibition of osteoclast differentiation is not well-documented. In this study, we assessed the effect of SFN on osteoclast differentiation in vitro. SFN inhibited osteoclast differentiation in both bone marrow cells and RAW264.7 cells. Key molecules involved in the inhibitory effects of SFN on osteoclast differentiation were determined using a microarray analysis, which showed that SFN inhibits osteoclast-associated genes, such as osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells cytoplasmic-1, tartrate-resistant acid phosphatase, and cathepsin K. Moreover, the mRNA expression levels of the cell-cell fusion molecules dendritic cell specific transmembrane protein (DC-STAMP) and osteoclast stimulatory transmembrane protein (OC-STAMP) were strongly suppressed in cells treated with SFN. Furthermore, SFN increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1), a regulator of macrophage and osteoclast cell fusion. Thus, our data suggested that SFN significantly inhibits the cell-cell fusion molecules DC-STAMP and OC-STAMP by inducing the phosphorylation of STAT1 (Tyr701), which might be regulated by interactions with OSCAR.
Insights
Sulforaphane (SFN) from broccoli sprouts inhibits osteoclast differentiation by suppressing key genes like DC-STAMP and OC-STAMP. This broccoli compound also enhances STAT1 phosphorylation, impacting cell fusion processes.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Sulforaphane (SFN), an isothiocyanate from broccoli sprouts, exhibits anti-tumor, anti-inflammatory, and anti-oxidation properties.
- The precise molecular mechanisms by which SFN influences osteoclast differentiation remain incompletely understood.
Purpose of the Study:
- To investigate the inhibitory effects of SFN on osteoclast differentiation in vitro.
- To identify the key molecular targets and pathways affected by SFN during osteoclastogenesis.
Main Methods:
- Osteoclast differentiation was assessed in bone marrow cells and RAW264.7 cells treated with SFN.
- Microarray analysis was employed to identify differentially expressed genes.
- mRNA expression levels of specific genes and protein phosphorylation were analyzed.
Main Results:
- SFN significantly inhibited osteoclast differentiation in both cell types.
- SFN suppressed the expression of osteoclast-associated genes, including OSCAR, NFATc1, TRAP, and cathepsin K.
- SFN markedly reduced mRNA levels of cell-cell fusion molecules DC-STAMP and OC-STAMP.
- SFN treatment led to increased phosphorylation of STAT1 (Tyr701).
Conclusions:
- SFN effectively inhibits osteoclast differentiation by targeting crucial genes and cell fusion molecules.
- The mechanism involves the suppression of DC-STAMP and OC-STAMP, potentially mediated by STAT1 phosphorylation and interactions with OSCAR.

