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Tetrahydroxystilbene Glucoside Regulates Proliferation, Differentiation, and OPG/RANKL/M-CSF Expression in MC3T3-E1 Cells via the PI3K/Akt Pathway

College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
College of Life Science and Food Engineering, Hebei University of Engineering, Handan 056038, China
Author to whom correspondence should be addressed.
Molecules 2018, 23(9), 2306;
Received: 30 July 2018 / Revised: 31 August 2018 / Accepted: 6 September 2018 / Published: 10 September 2018
(This article belongs to the Special Issue Bioactive Molecules and Their Mechanisms of Action)
PDF [4101 KB, uploaded 10 September 2018]


Tetrahydroxystilbene glucoside (TSG) is a unique component of the bone-reinforcing herb Radix Polygoni Multiflori Preparata (RPMP). It has the ability to promote bone formation and protect osteoblasts. However, the underlying mechanism remains unclear. To better understand its biological function, we determined TSG’s effect on murine pre-osteoblastic MC3T3-E1 cells by the MTT assay, flow cytometry, FQ-PCR, Western blot, and ELISA. The results showed that TSG caused an elevation of the MC3T3-E1 cell number, the number of cells in the S phase, and the mRNA levels of the runt-related transcription factor-2 (Runx2), osterix (Osx), and collagen type I α1 (Col1a1). In addition, the osteoprotegerin (OPG) mRNA level was up-regulated, while the nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) mRNA levels were down-regulated by TSG. Furthermore, TSG activated the phosphoinosmde-3-kinase/protein kinase B (also known as PI3K/Akt) pathway, and blocking this pathway by the inhibitor LY-294002 could impair TSG’s functions in relation to the MC3T3-E1 cells. In conclusion, TSG could activate the PI3K/Akt pathway and thus promote MC3T3-E1 cell proliferation and differentiation, and influence OPG/RANKL/M-CSF expression. TSG merits further investigation as a potential therapeutic agent for osteoporosis treatment. View Full-Text
Keywords: tetrahydroxystilbene glucoside; osteoblast; PI3K/Akt; herbal medicine; osteoporosis tetrahydroxystilbene glucoside; osteoblast; PI3K/Akt; herbal medicine; osteoporosis

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Fan, Y.-S.; Li, Q.; Hamdan, N.; Bian, Y.-F.; Zhuang, S.; Fan, K.; Liu, Z.-J. Tetrahydroxystilbene Glucoside Regulates Proliferation, Differentiation, and OPG/RANKL/M-CSF Expression in MC3T3-E1 Cells via the PI3K/Akt Pathway. Molecules 2018, 23, 2306.

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