Knockdown of LAP2α inhibits osteogenic differentiation of human adipose-derived stem cells by activating NE-κB

Background: Lamina-associated polypeptide 2 alpha (LAP2 alpha) is a nucleoplasmic protein that has been involved in the regulation of the cell cycle, gene transcription, and adult stem cell function. LAP2 alpha down-regulation is linked to age-related osteoporosis and bone deformities; however, the underlying mechanisms remain obscure. The present study aimed to elucidate the function of LAP2 alpha in the osteogenic differentiation of human adipose-derived stem cells (hASCs), which are attractive sources for bone tissue engineering. Methods: The expression of LAP2 alpha during the osteogenic differentiation of hASCs was detected firstly. A loss of function investigation was then carried out to characterize the function of LAP2 alpha in osteogenic differentiation of hASCs both in vitro and in vivo. Moreover, RNA-sequences, western blotting, and confocal analyses were performed to clarify the molecular mechanism of LAP2 alpha-regulated osteogenesis. Results: We found that LAP2 alpha expression was upregulated upon osteogenic induction. Both in vitro and in vivo experiments indicated that LAP2 alpha knockdown resulted in impaired osteogenic differentiation of hASCs. Mechanistically, we revealed that LAP2 alpha deficiency activated nuclear factor kappa B (NF-kappa B) signaling by controlling the cytoplasmic-nuclear translocation of p65. Conclusions: Collectively, our findings revealed that LAP2 alpha functions as an essential regulator for osteogenesis of hASCs by modulating NE-kappa B signaling, thus providing novel insights for mesenchymal stem cell-mediated bone tissue engineering.