在骨感染中,Piezo1促进M1巨噬细胞极化并损害成骨分化。

IF 4.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Rong-Shen Yang , Shuan-Ji Ou , Wei Zeng , Yu-Dun Qu , Jia-Xuan Li , Jiang-Ping Wen , Jia-Bao Liu , Chang-Liang Xia , Yong Qi , Chang-Peng Xu
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引用次数: 0

摘要

背景:骨感染引起强烈的炎症反应,导致骨再生受损,其中巨噬细胞通过Piezo1感知机制信号并调节炎症微环境中的免疫反应。尽管如此,在骨感染过程中,Piezo1在巨噬细胞中的调节作用仍然难以捉摸。方法:建立感染性骨缺损大鼠模型,进行整体RNA测序和单细胞RNA测序。从受感染的人骨和受感染的大鼠骨髓腔组织中收集组织进行体内验证。利用小鼠单核巨噬细胞和小鼠骨髓间充质干细胞进行了间接共培养细胞实验,进行了体外验证。结果:感染时骨髓巨噬细胞中Piezo1表达上调,驱动M1极化和炎性细胞因子分泌,引发PANoptosis,使骨髓间充质干细胞成骨分化受损。Piezo1抑制减弱了这些作用,证实了其调节作用。结论:感染过程中炎症微环境下,巨噬细胞中Piezo1表达增加,介导巨噬细胞向M1极化和促炎细胞因子分泌,诱导PANoptosis,损害骨髓间充质干细胞成骨分化。靶向piezo1介导的巨噬细胞和骨髓间充质干细胞之间的串扰为骨感染中骨再生的恢复提供了一种新的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Piezo1 promotes M1 macrophage polarization and impairs osteogenic differentiation in bone infection

Background

Bone infection induces a strong inflammatory response and leads to impaired bone regeneration, in which macrophages sense mechanistic signals and modulate immune responses in the inflammatory microenvironment through Piezo1. Nonetheless, the regulatory role of Piezo1 in macrophages during bone infection remains elusive.

Methods

Rat models of infected bone defects were established for bulk RNA sequencing and single-cell RNA sequencing. Tissues were collected from infected human bones and infected bone marrow cavity tissues of rats for in vivo validation. Indirect co-culture cell experiments were conducted using mouse mononuclear macrophages and mouse bone marrow mesenchymal stem cells for in virto validation.

Results

Piezo1 was upregulated in bone marrow macrophages during infection, driving M1 polarization and inflammatory cytokine secretion, which triggered PANoptosis and impaired the osteogenic differentiation of bone marrow mesenchymal stem cells. Piezo1 inhibition attenuated these effects, confirming its regulatory role.

Conclusions

Within the inflammatory microenvironment during infection, Piezo1 expression is increased in macrophages and mediates macrophage polarization toward M1 and pro-inflammatory cytokine secretion, inducing PANoptosis and impairing osteogenic differentiation in bone marrow mesenchymal stem cells. Targeting Piezo1-mediated crosstalk between macrophages and bone marrow mesenchymal stem cells offers a novel strategy for restoring bone regeneration in bone infection.
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来源期刊
CiteScore
12.30
自引率
0.00%
发文量
218
审稿时长
32 days
期刊介绍: BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.
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