Knockdown of LAP2? inhibits osteogenic differentiation of human adipose-derived stem cells by activating NF-?B.

ABSTRACT: BACKGROUND:Lamina-associated polypeptide 2? (LAP2?) is a nucleoplasmic protein that has been involved in the regulation of the cell cycle, gene transcription, and adult stem cell function. LAP2? 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? in the osteogenic differentiation of human adipose-derived stem cells (hASCs), which are attractive sources for bone tissue engineering. METHODS:The expression of LAP2? during the osteogenic differentiation of hASCs was detected firstly. A loss of function investigation was then carried out to characterize the function of LAP2? 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?-regulated osteogenesis. RESULTS:We found that LAP2? expression was upregulated upon osteogenic induction. Both in vitro and in vivo experiments indicated that LAP2? knockdown resulted in impaired osteogenic differentiation of hASCs. Mechanistically, we revealed that LAP2? deficiency activated nuclear factor kappa B (NF-?B) signaling by controlling the cytoplasmic-nuclear translocation of p65. CONCLUSIONS:Collectively, our findings revealed that LAP2? functions as an essential regulator for osteogenesis of hASCs by modulating NF-?B signaling, thus providing novel insights for mesenchymal stem cell-mediated bone tissue engineering.

SUBMITTER: Tang Y 

PROVIDER: S-EPMC7329510 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature