title: Ginsenoside-Rb2 inhibits dexamethasone-induced apoptosis through promotion of GPR120 induction in bone marrow-derived mesenchymal stem cells.
abstract: Apoptosis of bone marrow-derived mesenchymal stem cells (BMMSCs) is an essential pathogenic factor of osteoporosis. Ginsenoside-Rb2 (Rb2), a 20(S)-protopanaxadiol glycoside extracted from ginseng, is a potent treatment for bone loss, which raises interest regarding the bone metabolism area. In the present study, we found that dose-response Rb2 inhibited high dosage of dexamethasone (Dex)-induced apoptosis in primary murine BMMSCs. Interestingly, Rb2 promoted GPR120 induction, which is the unsaturated long-chain fatty acid receptor. We further confirmed that GPR120-specific ShRNA reversed the inhibition of Rb2 on Dex-induced apoptosis by activating caspase-3 and reducing cell viability. In addition, Rb2 notably increased phosphorylated ERK1/2 levels and Ras kinase activity dependently through the GPR120. The ERK1/2 activity-specific inhibitor U0126 remarkably blocked the Rb2-induced antiapoptotic effect in response to Dex-induced apoptosis. Together, dose-response Rb2 protected BMMSCs against Dex-induced apoptosis dependently by inducing GPR120 promoted Ras-ERK1/2 signaling pathway. Therefore, in the prevalence of the abuse of Dex in the clinic, our findings suggest for the first time that Rb2 is not only a key to understand the link between Chinese medicine and the pathology of osteoporosis but also an underlying target for the treatment of bone complications in the foreseeable future.
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Jie
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Zhang
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.forename: Yun-Shan
authors.initials: YS
authors.lastname: Guo
authors.forename: Zhen
authors.initials: Z
authors.lastname: Sun
authors.forename: Bo-Yuan
authors.initials: BY
authors.lastname: Wei
authors.forename: Yue-Hu
authors.initials: YH
authors.lastname: Han
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Zhuo-Jing
authors.initials: ZJ
authors.lastname: Luo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002478:Cells, Cultured; D003907:Dexamethasone / Q000633:toxicity; D036145:Ginsenosides / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C498007:FFAR4 protein, mouse; D036145:Ginsenosides; D043562:Receptors, G-Protein-Coupled; C048026:ginsenoside Rb2; D003907:Dexamethasone