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Sulfuretin induces osteoblast differentiation through activation of TGF-β signaling

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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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Correspondence to Kye Won Park.

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The authors declare no financial/commercial conflicts of interests.

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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

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