Butamben derivatives enhance BMP-2-stimulated commitment of C2C12 cells into osteoblasts with induction of voltage-gated potassium channel expression

As the primary step for ‘drug repositioning’, we evaluated the effect of 2000 drugs and drug candidates on the commitment of bi-potential mesenchymal precursor C2C12 cells into osteoblasts in the presence of bone morphogenetic protein (BMP)-2 and found that butamben enhanced BMP-2-stimulated induction of alkaline phosphatase, a biomarker of osteoblastogenesis. Investigating the underlying mechanism of its anabolic actions, we found anabolic action of its derivative (compound 4) relies on BMP-2 signaling and mRNA induction of BMPs and voltage-gated potassium channels.

Graphical abstractThe effect of butamben and its derivatives on the enhancement of BMP-2-stimulated osteoblast differentiation relies on BMP-2 signaling and mRNA induction of BMPs and Kv channels.Figure optionsDownload full-size imageDownload as PowerPoint slide