title: Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells.
abstract: Although previous studies have demonstrated that BMP9 is highly capable of inducing osteogenic differentiation of mesenchymal stem cells, the molecular mechanism involved remains to be fully elucidated. In this study, we showed that BMP9 simultaneously promotes the activation of Smad1/5/8, p38 and ERK1/2 in C3H10T1/2 cells. Knockdown of Smad4 with RNA interference reduced nuclear translocation of Smad1/5/8, and disrupted BMP9-induced osteogenic differentiation. BMP9-induced osteogenic differentiation was blocked by p38 inhibitor SB203580, whereas enhanced by ERK1/2 inhibitor PD98059. SB203580 decreased BMP9-activated Smads singling, and yet PD98059 stimulated Smads singling in C3H10T1/2 cells. The effects of inhibitor were reproduced with adenovirus expressing siRNA targeted p38 and ERK1/2, respectively. Taken together, our findings revealed that Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation. Also, it is noteworthy that p38 and ERK1/2 may play opposing regulatory roles in mediating BMP9-induced osteogenic differentiation of C3H10T1/2 cells.
authors.affiliation: Key Laboratory of Diagnostic Medicine, Chinese Ministry of Education, Chongqing Medical University, Chongqing, PR China.
authors.forename: Dao-jing
authors.initials: DJ
authors.lastname: Xu
authors.forename: Ying-ze
authors.initials: YZ
authors.lastname: Zhao
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Juan-wen
authors.initials: JW
authors.lastname: He
authors.forename: Ya-guang
authors.initials: YG
authors.lastname: Weng
authors.forename: Jin-yong
authors.initials: JY
authors.lastname: Luo
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D055427:Growth Differentiation Factor 2 / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; C526108:Gdf2 protein, mouse; D055427:Growth Differentiation Factor 2; D034741:RNA, Small Interfering; D051785:Smad Proteins; D008156:Luciferases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases