title: Salidroside induces neuronal differentiation of mouse mesenchymal stem cells through Notch and BMP signaling pathways.
abstract: 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.
authors.affiliation: Institute of Orthopedics, General Hospital of Lanzhou Military Command of the PLA, Key Laboratory of Stem Cells and Gene Medicine of Gansu Province, Lanzhou, Gansu 730050, China. Electronic address: zhao6703@aliyun.com.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Zhao
authors.affiliation: Department of Histology and Embryology, School of Basic Medicine, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou, Gansu 730000, China. Electronic address: qishn@lzu.edu.cn.
authors.forename: She-Ning
authors.initials: SN
authors.lastname: Qi
authors.affiliation: Institute of Orthopedics, General Hospital of Lanzhou Military Command of the PLA, Key Laboratory of Stem Cells and Gene Medicine of Gansu Province, Lanzhou, Gansu 730050, China.
authors.forename: Ju-Zi
authors.initials: JZ
authors.lastname: Dong
authors.affiliation: Institute of Orthopedics, General Hospital of Lanzhou Military Command of the PLA, Key Laboratory of Stem Cells and Gene Medicine of Gansu Province, Lanzhou, Gansu 730050, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Ha
authors.affiliation: Institute of Orthopedics, General Hospital of Lanzhou Military Command of the PLA, Key Laboratory of Stem Cells and Gene Medicine of Gansu Province, Lanzhou, Gansu 730050, China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Li
authors.affiliation: Institute of Orthopedics, General Hospital of Lanzhou Military Command of the PLA, Key Laboratory of Stem Cells and Gene Medicine of Gansu Province, Lanzhou, Gansu 730050, China.
authors.forename: Quan-Wei
authors.initials: QW
authors.lastname: Zhang
authors.affiliation: Institute of Orthopedics, General Hospital of Lanzhou Military Command of the PLA, Key Laboratory of Stem Cells and Gene Medicine of Gansu Province, Lanzhou, Gansu 730050, China.
authors.forename: Yin-Shu
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Institute of Orthopedics, General Hospital of Lanzhou Military Command of the PLA, Key Laboratory of Stem Cells and Gene Medicine of Gansu Province, Lanzhou, Gansu 730050, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
authors.affiliation: Institute of Orthopedics, General Hospital of Lanzhou Military Command of the PLA, Key Laboratory of Stem Cells and Gene Medicine of Gansu Province, Lanzhou, Gansu 730050, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D017931:DNA Primers; D005960:Glucosides / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D005960:Glucosides; D010636:Phenols; D051880:Receptors, Notch; C009172:rhodioloside
keywords: Bone morphogenetic proteins (BMP) signaling pathway; Differentiation; Mesenchymal stem cells; Notch signaling pathway; Salidroside