Implication of CXCR2-Src axis in the angiogenic and osteogenic effects of FP-TEB.

IF 6.4 1区医学 Q1 CELL & TISSUE ENGINEERING

npj Regenerative Medicine Pub Date : 2024-09-20 DOI:10.1038/s41536-024-00364-0

Sihao He, Tianyong Hou, Jiangling Zhou, Bo Yu, Juan Cai, Fei Luo, Jianzhong Xu, Junchao Xing

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引用次数: 0

Abstract

Application of tissue-engineered bones (TEBs) is hindered by challenges associated with incorporated viable cells. Previously, we employed freeze-drying techniques on TEBs to devitalize mesenchymal stem cells (MSCs) while preserving functional proteins, yielding functional proteins-based TEBs (FP-TEBs). Here, we aimed to elucidate their in vivo angiogenic and osteogenic capabilities and the mechanisms. qPCR arrays were employed to evaluate chemokines and receptors governing EC migration. Identified C-X-C chemokine receptors (CXCRs) were substantiated using shRNAs, and the pivotal role of CXCR2 was validated via conditional knockout mice. Finally, signaling molecules downstream of CXCR2 were identified. Additionally, Src, MAP4K4, and p38 MAPK were identified indispensable for CXCR2 function. Further investigations revealed that regulation of p38 MAPK by Src was mediated by MAP4K4. In conclusion, FP-TEBs promoted EC migration, angiogenesis, and osteogenesis via the CXCR2-Src-Map4k4-p38 MAPK axis.

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CXCR2-Src轴在FP-TEB的血管生成和成骨效应中的作用。

组织工程骨骼（TEBs）的应用受到了与纳入可存活细胞相关的挑战的阻碍。此前，我们采用冷冻干燥技术使间充质干细胞（MSCs）失去活性，同时保留了功能蛋白，从而获得了基于功能蛋白的 TEBs（FP-TEBs）。在此，我们旨在阐明其体内血管生成和成骨能力及其机制。我们采用 qPCR 阵列来评估影响EC迁移的趋化因子和受体。利用 shRNA 验证了已识别的 C-X-C 趋化因子受体（CXCR），并通过条件性基因敲除小鼠验证了 CXCR2 的关键作用。最后，确定了 CXCR2 下游的信号分子。此外，还发现了对 CXCR2 功能不可或缺的 Src、MAP4K4 和 p38 MAPK。进一步研究发现，Src 对 p38 MAPK 的调节是由 MAP4K4 介导的。总之，FP-TEBs 通过 CXCR2-Src-Map4k4-p38 MAPK 轴促进了 EC 迁移、血管生成和成骨。

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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来源期刊

npj Regenerative Medicine Engineering-Biomedical Engineering

CiteScore

10.00

自引率

1.40%

发文量

审稿时长

12 weeks

期刊介绍： Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.