Actin plays fundamental roles in both the cytoplasm and the cell nucleus. In the nucleus, β‐actin regulates neuronal reprogramming by consolidating a heterochromatin landscape required for transcription of neuronal gene programs, yet it remains unknown whether it has a role in other differentiation models. To explore the potential roles of β‐actin in osteogenesis, β‐actin wild‐type (WT) and β‐actin knockout (KO) mouse embryonic fibroblasts (MEFs) are reprogrammed to osteoblast‐like cells using small molecules in vitro. It is discovered that loss of β‐actin leads to an accelerated mineralization phenotype (hypermineralization), accompanied with enhanced formation of extracellular hydroxyapatite microcrystals, which originate in the mitochondria in the form of microgranules. This phenotype is a consequence of rapid upregulation of mitochondrial genes including those involved in oxidative phosphorylation (OXPHOS) in reprogrammed KO cells. It is further found that osteogenic gene programs are differentially regulated between WT and KO cells, with clusters of genes exhibiting different temporal expression patterns. A novel function for β‐actin in osteogenic reprogramming through a mitochondria‐based mechanism that controls cell‐mediated mineralization is proposed.

中文翻译：

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β-肌动蛋白的丢失导致成骨重编程过程中成骨细胞分化基因的加速矿化和失调

肌动蛋白在细胞质和细胞核中都发挥着重要作用。在细胞核中，β-肌动蛋白通过巩固神经元基因程序转录所需的异染色质景观来调节神经元重编程，但尚不清楚它是否在其他分化模型中发挥作用。为了探索β-肌动蛋白在成骨中的潜在作用，使用小分子在体外将β-肌动蛋白野生型（WT）和β-肌动蛋白敲除（KO）小鼠胚胎成纤维细胞（MEF）重编程为成骨细胞样细胞。研究发现，β-肌动蛋白的缺失会导致矿化表型加速（矿化过度），同时细胞外羟基磷灰石微晶的形成增强，这些微晶以微粒形式起源于线粒体。这种表型是线粒体基因快速上调的结果，包括重编程 KO 细胞中参与氧化磷酸化 (OXPHOS) 的基因。进一步发现，成骨基因程序在WT和KO细胞之间受到差异性调节，基因簇表现出不同的时间表达模式。提出了β-肌动蛋白通过基于线粒体的机制控制细胞介导的矿化在成骨重编程中的新功能。