DLL1/NOTCH1 signaling pathway maintain angiogenesis in meniscus development and degeneration

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-05-19 DOI:10.1016/j.biocel.2024.106589

Fangzhou Liu , Hao Sun , Deng Li , Junming Huang , Meiyi Chen, Xiaobin Lin, Jie Xu, Ruofan Ma

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Abstract

Objectives

The decline in vascular capacity within the meniscus is a well-documented phenomenon during both development and degeneration. Maintaining vascular integrity has been proposed as a potential therapeutic strategy for osteoarthritis. Therefore, our study aims to investigate the characteristics of endothelial cells and blood vessels in embryonic and degenerated meniscus tissues.

Methods

Human embryonic and mature menisci were used for histological analyses. Single-cell RNA sequencing was used to identify cell clusters and their significant genes in embryo meniscus to uncover characteristic of endothelial cells. Computer analysis and various staining techniques were used to characterize vessels in development and osteoarthritis meniscus.

Results

Vessels structure first observed in E12w and increasing in E14w. Vessels were veins majorly and arteries growth in E35w. Endothelial cells located not only perivascular but also in the surface of meniscus. The expression of DLL1 was observed to be significantly altered in endothelial cells within the vascular network that failed to form. Meniscus tissues affected by osteoarthritis, characterized by diminished vascular capacity, displayed reduced levels of DLL1 expression. Experiment in vitro confirmed DLL1/NOTCH1 be vital to angiogenesis.

Conclusion

Lack of DLL1/NOTCH1 signaling pathway was mechanism of vascular declination in development and degenerated meniscus.

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DLL1/NOTCH1信号通路维持半月板发育和退化过程中的血管生成

目的：半月板内血管容量的下降是发育和退化过程中的一个有据可查的现象。保持血管完整性已被认为是骨关节炎的一种潜在治疗策略。因此，我们的研究旨在调查胚胎期和退化期半月板组织中内皮细胞和血管的特征。方法：对人类胚胎和成熟的半月板进行组织学分析，利用单细胞 RNA 测序技术识别胚胎半月板中的细胞群及其重要基因，从而揭示内皮细胞的特征。计算机分析和各种染色技术被用来描述发育期和骨关节炎半月板中血管的特征：结果：在E12w期首次观察到血管结构，在E14w期逐渐增加。血管以静脉为主，在 E35w 生长为动脉。内皮细胞不仅位于血管周围，而且位于半月板表面。在未能形成血管网的内皮细胞中，观察到 DLL1 的表达发生了显著变化。受骨关节炎影响的半月板组织，其特点是血管能力减弱，DLL1的表达水平也随之降低。体外实验证实，DLL1/NOTCH1 对血管生成至关重要：结论：DLL1/NOTCH1 信号通路的缺乏是发育和退化的半月板血管衰退的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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