Activation of JNKs is essential for BMP9-induced osteogenic differentiation of mesenchymal stem cells

Abstract

Although BMP9 is highly capable of promoting osteogenicdifferentiation of mesenchymal stem cell (MSCs), the molecularmechanism involved remains to be fully elucidated. Here, weexplore the possible involvement and detail role of JNKs (c-JunN-terminal kinases) in BMP9-induced osteogenic differentiationof MSCs. It was found that BMP9 stimulated the activation ofJNKs in MSCs. BMP9-induced osteogenic differentiation ofMSCs was dramatically inhibited by JNKs inhibitor SP600125.Moreover, BMP9-activated Smads signaling was decreased bySP600125 treatment in MSCs. The effects of inhibitor arereproduced with adenoviruses expressing siRNA targeted JNKs.Taken together, our results revealed that JNKs was activated inBMP9-induced osteogenic differentiation of MSCs. What ismost noteworthy, however, is that inhibition of JNKs activityresulted in reduction of BMP9-induced osteogenic differentiationof MSCs, implying that activation of JNKs is essential forBMP9 osteoinductive activity. [BMB Reports 2013; 46(8):422-427]

Keywords

• BMP9
• Bone morphogenetic proteins
• Mesenchymal stem cells
• Mitogen activated protein kinases
• Osteogenic differentiation