Piezo1-mediated M2 macrophage mechanotransduction enhances bone formation through secretion and activation of transforming growth factor-β1
© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:56 |
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| Enthalten in: |
Cell proliferation - 56(2023), 9 vom: 15. Sept., Seite e13440 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cai, Guanhui [VerfasserIn] |
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| Links: |
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| Themen: |
Ion Channels |
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| Anmerkungen: |
Date Completed 04.09.2023 Date Revised 05.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/cpr.13440 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 650 | 7 | |a Piezo1 protein, mouse |2 NLM | |
| 650 | 7 | |a Ion Channels |2 NLM | |
| 700 | 1 | |a Lu, Yahui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Weijie |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yingyi |e verfasserin |4 aut | |
| 700 | 1 | |a Ruan, Xiaolei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hongyu |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Lian |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Zhaolan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Gen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hengwei |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Minglong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei-Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hua |e verfasserin |4 aut | |
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