Piezo1-mediated M2 Macrophage Mechanotransduction Enhances Bone Formation Through Secretion and Activation of Transforming Growth Factor-β1

Overview

Journal Cell Prolif

Date 2023 Mar 7

PMID 36880296

Authors

Guanhui Cai

Yahui Lu

Weijie Zhong

Ting Wang

Yingyi Li

Xiaolei Ruan

Hongyu Chen

Lian Sun

Zhaolan Guan

Gen Li

Hengwei Zhang

Wen Sun

Minglong Chen

Wei-Bing Zhang

Hua Wang

Affiliations

Soon will be listed here.

Abstract

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.

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