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. 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. 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. 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.

中文翻译：

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敲低 LAP2α 通过激活 NF-κB 来抑制人脂肪干细胞的成骨分化。

纤层相关多肽 2α (LAP2α) 是一种核质蛋白，参与调节细胞周期、基因转录和成体干细胞功能。LAP2α 下调与年龄相关的骨质疏松症和骨骼畸形有关；然而，潜在的机制仍然模糊不清。本研究旨在阐明 LAP2α 在人类脂肪干细胞 (hASCs) 的成骨分化中的功能，这是骨组织工程的有吸引力的来源。首先检测hASCs成骨分化过程中LAP2α的表达。然后进行功能丧失研究以表征 LAP2α 在体外和体内 hASCs 成骨分化中的功能。此外，RNA 序列、蛋白质印迹、并进行了共聚焦分析以阐明 LAP2α 调节成骨的分子机制。我们发现 LAP2α 表达在成骨诱导后上调。体外和体内实验均表明 LAP2α 敲低导致 hASCs 的成骨分化受损。从机制上讲，我们揭示了 LAP2α 缺乏通过控制 p65 的细胞质 - 核易位来激活核因子 kappa B (NF-κB) 信号传导。总的来说，我们的研究结果表明 LAP2α 通过调节 NF-κB 信号传导作为 hASCs 成骨的重要调节因子，从而为间充质干细胞介导的骨组织工程提供了新的见解。体外和体内实验均表明 LAP2α 敲低导致 hASCs 的成骨分化受损。从机制上讲，我们揭示了 LAP2α 缺乏通过控制 p65 的细胞质 - 核易位来激活核因子 kappa B (NF-κB) 信号传导。总的来说，我们的研究结果表明 LAP2α 通过调节 NF-κB 信号传导作为 hASCs 成骨的重要调节因子，从而为间充质干细胞介导的骨组织工程提供了新的见解。体外和体内实验均表明 LAP2α 敲低导致 hASCs 的成骨分化受损。从机制上讲，我们揭示了 LAP2α 缺乏通过控制 p65 的细胞质 - 核易位来激活核因子 kappa B (NF-κB) 信号传导。总的来说，我们的研究结果表明 LAP2α 通过调节 NF-κB 信号传导作为 hASCs 成骨的重要调节因子，从而为间充质干细胞介导的骨组织工程提供了新的见解。