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 highlycapable of inducing osteogenic differentiation of mesenchymalstem cells, the molecular mechanism involved remains to be fullyelucidated. In this study, we showed that BMP9 simultaneouslypromotes the activation of Smad1/5/8, p38 and ERK1/2 in C3H10T1/2cells. Knockdown of Smad4 with RNA interference reduced nucleartranslocation of Smad1/5/8, and disrupted BMP9-inducedosteogenic differentiation. BMP9-induced osteogenic differentiationwas blocked by p38 inhibitor SB203580, whereas enhancedby ERK1/2 inhibitor PD98059. SB203580 decreased BMP9-activatedSmads singling, and yet PD98059 stimulated Smads singlingin C3H10T1/2 cells. The effects of inhibitor were reproduced withadenovirus expressing siRNA targeted p38 and ERK1/2, respectively.Taken together, our findings revealed that Smads, p38 andERK1/2 are involved in BMP9-induced osteogenic differentiation.Also, it is noteworthy that p38 and ERK1/2 may play opposing regulatoryroles in mediating BMP9-induced osteogenic differentiationof C3H10T1/2 cells. [BMB reports 2012; 45(4): 247-252]

Keywords

• Bone morphogenetic proteins
• Mesenchymal stem cells
• Mitogen activated protein kinases
• Osteogenic differentiation
• Smads