Faculty of Medicine and Health Sciences, Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada.
CHU Sainte-Justine Research Center, Montreal, QC, Canada.
Matrix Biol. 2024 Dec;134:23-29. doi: 10.1016/j.matbio.2024.08.010. Epub 2024 Sep 2.
Fibronectin (FN) serves as a critical organizer of extracellular matrix networks in two principal isoforms, the plasma FN and the cellular FN. While FN's pivotal role in various organ systems, including the blood vasculature, is well-established, its contribution to the development of the skeletal system is much less explored. Furthermore, the pathomechanisms of spondyloepiphyseal dysplasia caused by FN mutations remain elusive. In this minireview, we discuss findings from our recent two studies using i) an iPSC-based cell culture model to explore how FN mutations in spondyloepiphyseal dysplasia impact mesenchymal cell differentiation into chondrocytes and ii) conditional FN knockout mouse models to determine the physiological roles of FN isoforms during postnatal skeletal development. The data revealed that FN mutations cause severe intracellular and matrix defects in mesenchymal cells and impair their ability to differentiate into chondrocytes. The findings further demonstrate the important roles of both FN isoforms in orchestrating regulated chondrogenesis during skeletal development. We critically discuss the findings in the context of the existing literature.
纤连蛋白（FN）有两种主要的同工型，即血浆 FN 和细胞 FN，作为细胞外基质网络的重要组织者。虽然 FN 在包括血液脉管系统在内的各种器官系统中的关键作用已得到充分证实，但它对骨骼系统发育的贡献却鲜为人知。此外，由 FN 突变引起的脊椎骨骺发育不良的发病机制仍难以捉摸。在这篇简评中，我们讨论了我们最近两项研究的结果：i）使用基于 iPSC 的细胞培养模型探索脊椎骨骺发育不良中的 FN 突变如何影响间充质细胞向软骨细胞的分化；ii）使用条件性 FN 敲除小鼠模型确定 FN 同工型在出生后骨骼发育过程中的生理作用。数据表明，FN 突变导致间充质细胞的严重细胞内和基质缺陷，并损害其分化为软骨细胞的能力。这些发现进一步证明了两种 FN 同工型在协调骨骼发育过程中的受调控的软骨生成中的重要作用。我们在现有文献的背景下批判性地讨论了这些发现。
