title: Physcion-8-O-beta-D-glucopyranoside enhances the commitment of mouse mesenchymal progenitors into osteoblasts and their differentiation: Possible involvement of signaling pathways to activate BMP gene expression.
abstract: Here, we show the involvement of signaling pathways to induce the gene expression of bone morphogenetic protein (BMP) in the osteogenic activity of physcion-8-O-beta-D-glucopyranoside (physcion-Glu); it stimulated osteoblast differentiation in mouse osteoblast MC3T3-E1 subclone 4 cells and induced BMP-2 gene expression and activation of Akt and ERK/MAP kinases. Physcion-Glu-induced BMP-2 expression and mineralization were attenuated by LY294002, an inhibitor of PI3K that lies upstream of Akt and MAP kinases, suggesting that physcion-Glu induces osteoblast differentiation via PI3K-Akt/MAP kinase signaling pathways, which play important roles in inducing BMP-2 gene expression. Physcion-Glu also enhanced BMP-2-induced commitment of mouse bi-potential mesenchymal precursor C2C12 cells into osteoblasts while inducing the transcription of several osteogenic BMP isoforms, such as BMP-2, -4, -7, and -9. Osteogenic synergy between BMP-2 and physcion-Glu was supported by the fact that noggin inhibited BMP-2 and physcion-Glu-induced alkaline phosphatase expression and activity. Considering that physcion-Glu induced Runx2 activity and the nuclear translocation of p-Smad, physcion-Glu could act by enhancing the BMP signaling pathway that induces Smad activation and translocation to activate Runx2. In conclusion, physcion-Glu could enhance the commitment of mesenchymal progenitors into osteoblasts and their differentiation by activating signaling pathways to induce BMP gene expression.
authors.affiliation: Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, Daejeon 305-600, Korea.
authors.forename: Su-Ui
authors.initials: SU
authors.lastname: Lee
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Choi
authors.forename: Young Sup
authors.initials: YS
authors.lastname: Kim
authors.forename: Sang-Joon
authors.initials: SJ
authors.lastname: Park
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kwak
authors.forename: Yong Ki
authors.initials: YK
authors.lastname: Min
authors.forename: Hyun-Nam
authors.initials: HN
authors.lastname: Kim
authors.forename: Kyung-Eun
authors.initials: KE
authors.lastname: Lim
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
authors.forename: Myungchull
authors.initials: M
authors.lastname: Rhee
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004642:Emodin / Q000031:analogs & derivatives* / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry* / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D055396:Bone Morphogenetic Protein 2; D002867:Chromones; D004642:Emodin; D005960:Glucosides; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C525719:Bmp2 protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C008905:physcione