Abstract
The identification and examination of potential determinants controlling the progression of cell fate toward osteoblasts can be intriguing subjects. In this study, the effects of sulfuretin, a major compound isolated from Rhus verniciflua Stokes, on osteoblast differentiation were investigated. Treatments of sulfuretin induced alkaline phosphatase (ALP) activity in mesenchymal C3H10T1/2 cells and mineralization in preosteoblast MC3T3-E1 cells. Pro-osteogenic effects of sulfuretin were consistently observed in freshly isolated primary bone marrow cells. In mechanical studies, sulfuretin specifically induced expression of TGF-β target genes, such as SMAD7 and PAI-1, but not other signaling pathway-related genes. Similar to the results of gene expression analysis, reporter assays further demonstrated TGF-β-specific induction by sulfuretin. Furthermore, disruption of TGF-β signaling using treatment with TGF-β-specific inhibitor, SB-431542, and introduction of SMAD2/3 small interfering RNA impaired the effects of sulfuretin in inducing ALP activity and expression of ALP mRNA. Together, these data indicate that the pro-osteogenic effects of sulfuretin are mediated through activation of TGF-β signaling, further supporting the potential of sulfuretin in the prevention of bone-related diseases such as bone fracture and osteoporosis.
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Abbreviations
- ALP:
-
Alkaline phosphatase
- OCN:
-
Osteocalcin
- OSX:
-
Osterix
- COL I:
-
Collagen I
- MSC:
-
Mesenchymal stem cells
- TGF-β1:
-
Transforming growth factor-β1
- WNT:
-
Wingless-int
- BMP:
-
Bone morphogenetic protein
- siRNA:
-
Small interfering RNA
- MTT:
-
3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
- DMSO:
-
Dimethylsulfoxide
- PCR:
-
Polymerase chain reaction
- BCIP:
-
5-Bromo-4-cholor-3-indolyl phosphate
- NBT:
-
Nitroblue tetrazolium
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Acknowledgments
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (NRF-2011-0014302, NRF-2013R1A1A2060447).
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No-Joon Song and So-Mi Kwon have contributed equally to this work.
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Song, NJ., Kwon, SM., Kim, S. et al. Sulfuretin induces osteoblast differentiation through activation of TGF-β signaling. Mol Cell Biochem 410, 55–63 (2015). https://doi.org/10.1007/s11010-015-2537-5
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DOI: https://doi.org/10.1007/s11010-015-2537-5