Stem Cells and Cell Therapy Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, Plaza de Cruces S/N, 48903 Barakaldo, Bizkaia, Spain.
Cells. 2020 May 26;9(6):1330. doi: 10.3390/cells9061330.
Lamin A/C, intermediate filament proteins from the nuclear lamina encoded by the 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 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.
核纤层蛋白 A/C（lamin A/C）是由 基因编码的核纤层中间丝蛋白，在将细胞骨架力的机械信号转导到细胞核中发挥核心作用。事实上，这个机械转导过程对于确保其他由 lamin A/C 介导的任务的正常运作是必不可少的：细胞核的结构支撑和基因表达的调节。因此，lamin A/C 对于间充质干细胞（MSC）的迁移和分化至关重要，MSC 是成骨细胞的前体细胞，从而影响骨稳态。骨形成是一个受化学和机械线索调节的复杂过程，这些线索来自周围的细胞外基质。MSCs 对调节 lamin A/C 表达水平的信号做出反应，从而适应其核形状和硬度。为了促进细胞迁移，MSCs 需要具有低 lamin A 含量的柔软核。相反，在成骨分化过程中，已知 lamin A/C 水平会增加。一些 突变对 MSCs 的迁移和成骨作用有负面影响，影响骨组织稳态并导致病理状况。本综述旨在通过讨论该领域的最新研究进展，描述这些概念，重点关注健康和病理观点下 lamin A/C 与 MSCs 功能和骨组织之间的关系。
