Lamin A/C, intermediate filament proteins from the nuclear lamina encoded by the LMNA gene, play a central role in mediating the mechanosignaling of cytoskeletal forces into nucleus. In fact, this mechanotransduction process is essential to ensure the proper functioning of other tasks also mediated by lamin A/C: the structural support of the nucleus and the regulation of gene expression. In this way, lamin A/C is fundamental for the migration and differentiation of mesenchymal stem cells (MSCs), the progenitors of osteoblasts, thus affecting bone homeostasis. Bone formation is a complex process regulated by chemical and mechanical cues, coming from the surrounding extracellular matrix. MSCs respond to signals modulating the expression levels of lamin A/C, and therefore, adapting their nuclear shape and stiffness. To promote cell migration, MSCs need soft nuclei with low lamin A content. Conversely, during osteogenic differentiation, lamin A/C levels are known to be increased. Several LMNA mutations present a negative impact in the migration and osteogenesis of MSCs, affecting bone tissue homeostasis and leading to pathological conditions. This review aims to describe these concepts by discussing the latest state-of-the-art in this exciting area, focusing on the relationship between lamin A/C in MSCs’ function and bone tissue from both, health and pathological points of view.

中文翻译：

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Lamin A / C在骨髓间充质干细胞迁移和分化中的关键作用。

Lamin A / C，LMNA编码的核层中的中间丝蛋白基因在介导细胞骨架力向核的机械信号传递中起着核心作用。实际上，这种机械转导过程对于确保其他由lamin A / C介导的其他任务的正常功能至关重要：核的结构支持和基因表达的调节。通过这种方式，层粘蛋白A / C对于成骨细胞的祖细胞间充质干细胞（MSC）的迁移和分化至关重要，从而影响了骨稳态。骨形成是一个复杂的过程，受周围细胞外基质的化学和机械提示调节。MSC响应信号调节层粘蛋白A / C的表达水平，因此适应其核形状和硬度。为了促进细胞迁移，MSC需要薄层A含量低的软核。反过来，在成骨分化过程中，已知lamin A / C水平升高。一些LMNA突变对MSC的迁移和成骨作用产生负面影响，影响骨骼组织的稳态并导致病理状况。这篇综述旨在通过讨论这一激动人心的领域中的最新技术来描述这些概念，重点从健康和病理的角度着眼于MSC功能中的层状A / C与骨骼组织之间的关系。