α-细小蛋白控制软骨细胞柱的形成并调节长骨的发育。

IF 14.3 1区 医学 Q1 CELL & TISSUE ENGINEERING
Jifan Yuan, Ling Guo, Jiaxin Wang, Zhongjun Zhou, Chuanyue Wu
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引用次数: 1

摘要

软骨内骨化需要对软骨细胞的增殖、分化、存活和组织进行适当的控制。在这里,我们发现从小鼠四肢敲除α-细小蛋白,一种整合素相关的局灶性粘附蛋白,会导致软骨内骨化和侏儒症的缺陷。突变长骨较短但较宽,生长板变得杂乱无章,尤其是在增殖区。通过骨外植体培养的双光子延时成像,我们提供了直接证据,表明α-细小蛋白调节软骨细胞旋转,这是软骨细胞形成柱状结构所必需的过程。此外,α-细小蛋白的缺失增加了双核化,增加了细胞死亡,并导致成熟生长板的休息区扩张。单细胞RNA-seq分析显示,生长板的所有三个区域(即静息区、增殖区和肥大区)的转录组都发生了变化。我们的研究结果证明了α-细小蛋白在长骨发育中的关键作用,并阐明了α-微小蛋白调节长骨纵向生长的细胞机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

α-parvin controls chondrocyte column formation and regulates long bone development.

α-parvin controls chondrocyte column formation and regulates long bone development.

α-parvin controls chondrocyte column formation and regulates long bone development.

α-parvin controls chondrocyte column formation and regulates long bone development.

Endochondral ossification requires proper control of chondrocyte proliferation, differentiation, survival, and organization. Here we show that knockout of α-parvin, an integrin-associated focal adhesion protein, from murine limbs causes defects in endochondral ossification and dwarfism. The mutant long bones were shorter but wider, and the growth plates became disorganized, especially in the proliferative zone. With two-photon time-lapse imaging of bone explant culture, we provide direct evidence showing that α-parvin regulates chondrocyte rotation, a process essential for chondrocytes to form columnar structure. Furthermore, loss of α-parvin increased binucleation, elevated cell death, and caused dilation of the resting zones of mature growth plates. Single-cell RNA-seq analyses revealed alterations of transcriptome in all three zones (i.e., resting, proliferative, and hypertrophic zones) of the growth plates. Our results demonstrate a crucial role of α-parvin in long bone development and shed light on the cellular mechanism through which α-parvin regulates the longitudinal growth of long bones.

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来源期刊
Bone Research
Bone Research CELL & TISSUE ENGINEERING-
CiteScore
20.00
自引率
4.70%
发文量
289
审稿时长
20 weeks
期刊介绍: Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.
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