Akt phosphorylates and regulates the osteogenic activity of Osterix

Osterix (Osx), a zinc-finger transcription factor is required for osteoblast differentiation and new bone formation during embryonic development. Akt is a member of the serine/threonine-specific protein kinase and plays important roles in osteoblast differentiation. The function of Osterix can be also modulated by post-translational modification. But, the precise molecular signaling mechanisms between Osterix and Akt are not known. In this study, we investigated the potential regulation of Osterix function by Akt in osteoblast differentiation. We found that Akt phosphorylates Osterix and that Akt activation increases protein stability, osteogenic activity and transcriptional activity of Osterix. We also found that BMP-2 increases the protein level of Osterix in an Akt activity-dependent manner. These results suggest that Akt activity enhances the osteogenic function of Osterix, at least in part, through protein stabilization and that BMP-2 regulates the osteogenic function of Osterix, at least in part, through Akt.

► Akt interacts with Osterix endogenously.
► Over-expressed Akt1 induces the phosphorylation of Akt target phosphorylation site(s) and increases the protein level of endogenous Osterix.
► Wild type Akt1, but not the kinase-defective Akt1, prolongs the half-life of Osterix.
► Akt1 enhances the transcriptional activity of Osterix in an Akt kinase activity-dependent manner.