Salidroside induces neuronal differentiation of mouse mesenchymal stem cells through Notch and BMP signaling pathways

• Published in: Food and chemical toxicology Vol. 71; pp. 60 - 67
• Main Authors: Zhao, Hong-Bin, Qi, She-Ning, Dong, Ju-Zi, Ha, Xiao-Qin, Li, Xiao-Yun, Zhang, Quan-Wei, Yang, Yin-Shu, Bai, Jie, Zhao, Ling
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2014; Elsevier
• Subjects: Animals; Base Sequence; Biological and medical sciences; Bone morphogenetic proteins (BMP) signaling pathway; Bone Morphogenetic Proteins - metabolism; Cell Differentiation - drug effects; Differentiation; DNA Primers; Drosophila; Food toxicology; Glucosides - pharmacology; Medical sciences; Mesenchymal stem cells; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Mice; Neurons - cytology; Neurons - drug effects; Notch signaling pathway; Phenols - pharmacology; Real-Time Polymerase Chain Reaction; Receptors, Notch - metabolism; Salidroside; Toxicology; Salidroside; Notch signaling pathway; Differentiation; Bone morphogenetic proteins (BMP) signaling pathway; Mesenchymal stem cells; Stem cell; Rodentia; Signal transduction; Vertebrata; Mammalia; Bone morphogenetic protein; Mouse; Animal
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2014.05.031

•Salidroside (SAL) inhibits the proliferation of mouse mesenchymal stem cells (D1).•SAL induces D1 cells to adopt neuronal phenotypes.•SAL-induced neuronal differentiation is down-regulated by Notch signaling pathway.•SAL-induced neuronal differentiation is up-regulated by BMP signaling pathway. Salidroside (p-hydroxyphenethyl-β-d-glucoside, SAL), a phenylpropanoid glycoside isolated from a popular traditional Chinese medicinal plant Rhodiola rosea L., possesses multiple pharmacological actions. Previous study showed that SAL could induce rat mesenchymal stem cells (MSCs) to differentiate into dopaminergic neurons and induce mouse MSCs D1 to differentiate into neuronal cells. However, the mechanisms of SAL-induced neuronal differentiation of MSCs still need investigation. In this study, we observed the effects of SAL on neuronal differentiation of D1 cells and the possible involvement of Notch and BMP signaling pathways. SAL inhibited the proliferation, induced neuronal phenotypes, and upregulated the expressions of neuronal-specific marker molecules, such as neuronal enolase 2 (Eno2/NSE), microtubule-associated protein 2 (MAP2), and beta 3 class III tubulin (Tubb3/β-tubulin III) in D1 cells. SAL not only downregulated the expressions of Notch1 and hairy enhancer of split 1 (Drosophila) (Hes1) but also upregulated the expression of Smad1/5/8 and its phosphorylation (p-Smad 1/5/8). The neuronal differentiation effects of SAL on D1 cells were promoted by a Notch signaling antagonist, DAPT, but attenuated by a BMP signaling pathway antagonist, Noggin. Our findings suggest that SAL might be promising in inducing neuronal differentiation of mouse MSCs mediated by both Notch signaling pathway and BMP signaling pathway.