Macrophages are multifunctional immune system cells that are essential for the mechanical stimulation-induced control of metabolism. Piezo1 is a non-selective calcium channel expressed in multifarious tissues to convey mechanical signals. Here, a cellular model of tension was used to study the effect of mechanical stretch on the phenotypic transformation of macrophages and its mechanism. An indirect co-culture system was used to explore the effect of macrophage activation on bone marrow mesenchymal stem cells (BMSCs), and a treadmill running model was used to validate the mechanism in vivo for in vitro studies. p53 was acetylated and deacetylated by macrophages as a result of mechanical strain being detected by Piezo1. This process is able to polarize macrophages towards M2 and secretes transforming growth factor-beta (TGF-β1), which subsequently stimulates BMSCs migration, proliferation and osteogenic differentiation. Knockdown of Piezo1 inhibits the conversion of macrophages to the reparative phenotype, thereby affecting bone remodelling. Blockade of TGF-β I, II receptors and Piezo1 significantly reduced exercise-increased bone mass in mice. In conclusion, we showed that mechanical tension causes calcium influx, p53 deacetylation, macrophage polarization towards M2 and TGF-β1 release through Piezo1. These events support BMSC osteogenesis.

中文翻译：

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Piezo1 介导的 M2 巨噬细胞机械转导通过分泌和激活转化生长因子-β1 增强骨形成

巨噬细胞是多功能免疫系统细胞，对于机械刺激诱导的新陈代谢控制至关重要。Piezo1 是一种在多种组织中表达的非选择性钙通道，用于传递机械信号。在这里，利用张力的细胞模型来研究机械拉伸对巨噬细胞表型转变的影响及其机制。采用间接共培养系统探讨巨噬细胞活化对骨髓间充质干细胞（BMSCs）的影响，并采用跑台跑步模型验证体内机制以进行体外研究。由于 Piezo1 检测到机械应变，p53 被巨噬细胞乙酰化和脱乙酰化。该过程能够使巨噬细胞极化向 M2 并分泌转化生长因子-β (TGF-β1)，随后刺激 BMSC 迁移、增殖和成骨分化。Piezo1 的敲低会抑制巨噬细胞向修复表型的转化，从而影响骨重塑。阻断 TGF-β I、II 受体和 Piezo1 可显着降低小鼠运动增加的骨量。总之，我们发现机械张力导致钙流入、p53 脱乙酰化、巨噬细胞极化向 M2 以及通过 Piezo1 释放 TGF-β1。这些事件支持 BMSC 成骨。