NEDD4's effect on osteoblastogenesis potential of bone mesenchymal stem cells in rats concerned with PI3K/Akt pathway

Neural precursor cell expressed developmentally down-regulated 4 (NEDD4) is an E3 ubiquitin ligase implicated in craniofacial development. Emerging evidence suggests that NEDD4 may down-regulates Akt signaling, a key element of the PI3K/Akt pathway involved in cell differentiation. This study aimed to investigate NEDD4's role in bone mesenchymal stem cells (BMSCs) differentiation and its interaction with the PI3K/Akt pathway. BMSCs were isolated from SD rats, and NEDD4 expression increased during osteogenic differentiation. Silencing NEDD4 with siRNA elevated alkaline phosphatase (ALP), osteocalcin (OCN), Akt, and mTORC1 expression during induction, while subsequent treatment with LY294002 (a broad spectrum PI3K inhibitor) reduced Akt, mTORC1, ALP, and OCN levels. These findings suggest that NEDD4 may inhibit BMSCs differentiation by suppressing the PI3K/Akt pathway during osteogenesis.