title: Radix Dipsaci total saponins stimulate MC3T3-E1 cell differentiation via the bone morphogenetic protein-2/MAPK/Smad-dependent Runx2 pathway.
abstract: Radix Dipsaci total saponins (RTS) are primary active components of Radix Dipsaci, which is administered orally for the treatment of osteoporosis according to Chinese Medicine. RTS have also been shown to reduce the risk of bone fractures in rats. However, the detailed molecular mechanisms underlying their action remain elusive. In the present study, the ability of RTS to increase alkaline phosphatase activity, osteocalcin levels and the degree of mineralization was investigated in MC3T3‑E1 mouse osteoblast precursor cells. In addition, the associated molecular mechanism was detected. The results revealed that RTS exerted an effect on osteoblastic maturation and differentiation. Induction of differentiation by RTS was associated with an increase in the expression levels of bone morphogenetic protein‑2 (BMP‑2), phosphorylated (P)‑Smad1/5/8, P‑ERK1/2, P‑p38 and Runt‑related transcription factor 2 (Runx2). Blocking BMP‑2 expression with noggin significantly reduced the levels of osteoblastic differentiation and subsequently attenuated the expression levels of P‑Smad1/5/8, P‑ERK1/2, P‑p38 and Runx2. This indicated that RTS induced osteoblastic differentiation through BMP‑2/mitogen‑activated protein kinase/Smad1/5/8‑dependent Runx2 signaling pathways and that it may be a promising agent for enhancing bone formation.
authors.affiliation: Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, P.R. China.
authors.forename: Yin-Bo
authors.initials: YB
authors.lastname: Niu
authors.affiliation: Graduate School of Chang'an University, Xi'an, Shaanxi 710064, P.R. China.
authors.forename: Xiang-He
authors.initials: XH
authors.lastname: Kong
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Li
authors.affiliation: Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.affiliation: Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, P.R. China.
authors.forename: Ya-Lei
authors.initials: YL
authors.lastname: Pan
authors.affiliation: Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, P.R. China.
authors.forename: Chen-Rui
authors.initials: CR
authors.lastname: Li
authors.affiliation: Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, P.R. China.
authors.forename: Xiang-Long
authors.initials: XL
authors.lastname: Wu
authors.affiliation: Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, P.R. China.
authors.forename: Ting-Li
authors.initials: TL
authors.lastname: Lu
authors.affiliation: Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, P.R. China.
authors.forename: Qi-Bing
authors.initials: QB
authors.lastname: Mei
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D049851:Gastropoda / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse; D012503:Saponins; D051785:Smad Proteins; D015675:Osteocalcin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases