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

Abstract

Background: Lamina-associated polypeptide 2α (LAP2α) is a nucleoplasmic protein that has been involved in the regulation of the cell cycle, gene transcription, and adult stem cell function. LAP2α 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 LAP2α in the osteogenic differentiation of human adipose-derived stem cells (hASCs), which are attractive sources for bone tissue engineering. Methods: The expression of LAP2α during the osteogenic differentiation of hASCs was detected firstly. A loss of function investigation was then carried out to characterize the function of LAP2α 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 LAP2α-regulated osteogenesis. Results: We found that LAP2α expression was upregulated upon osteogenic induction. Both in vitro and in vivo experiments indicated that LAP2α knockdown resulted in impaired osteogenic differentiation of hASCs. Mechanistically, we revealed that LAP2α deficiency activated nuclear factor kappa B (NF-κB) signaling by controlling the cytoplasmic-nuclear translocation of p65. Conclusions: Collectively, our findings revealed that LAP2α functions as an essential regulator for osteogenesis of hASCs by modulating NF-κB signaling, thus providing novel insights for mesenchymal stem cell-mediated bone tissue engineering.

Classical isoforms of protein kinase C (PKC) and Akt regulate the osteogenic differentiation of human dental follicle cells via both β-catenin and NF-κB

“…4 e). This is in line with the results of other studies who showed that activation of NF-κB attenuates the osteogenic differentiation of precursor cells [ 38 – 40 ]. Activity of PKC is further related to the process of tooth eruption by stimulating the expression of tumor necrosis factor α (TNF-α) [ 41 ], which results in the activation of NF-κB [ 42 ].…”

Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity

“…Indeed, loss of Lap2α leads to inefficient cell-cycle arrest, and hyperproliferation of, for example, erythroid and epidermal progenitor cells in mice 26 . Another important role of Lap2α was shown recently in human adipose-derived stem cells (hASCs), where loss of Lap2α suppresses osteogenic differentiation of hASCs via activation of NF-κB transcription factor 30 . Moreover, loss of Lap2α impairs heart function, and results in deregulation of the cardiac transcription factors GATA4 and MEF2c 31 .…”

Functions and regulatory mechanisms of resting hematopoietic stem cells: a promising targeted therapeutic strategy

“…The deletion of LAP2α in mice can promote a proliferative stem cell phenotype in progenitor cells and delay stem cell differentiation [ 68 ]. LAP2α has also been found to act as an important regulator of osteogenic differentiation in human adipose stem cells (hASCs) through the regulation of the NF-κB signaling pathway, and knocking down LAP2α leads to impaired osteogenic hASC differentiation [ 69 ].…”