Effect of Piezo1 Channel-Mediated Mechanotransduction on Osteogenic Differentiation and Interleukin-6 Secretion in Bone Mesenchymal Stem Cells Under Tensile Strain
{"title":"Effect of Piezo1 Channel-Mediated Mechanotransduction on Osteogenic Differentiation and Interleukin-6 Secretion in Bone Mesenchymal Stem Cells Under Tensile Strain","authors":"Xu Yan, Su Fu, Ying Xie, Xuejian Wu","doi":"10.1166/jbn.2024.3730","DOIUrl":null,"url":null,"abstract":"Physical stimulation plays a crucial role in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs). However, the mechanotransductive mechanisms remain uncleared. Recent studies have suggested that the Piezo1 channel is essential for transforming mechanical\n signals. Therefore, we investigate the Piezo1-mediated mechanisms in mechanical strain-regulated MSC osteogenic differentiation and release of proinflammatory cytokines. The tensile strain was applied to rat MSCs cultured in a monolayer to induce mechanical strain. The immuno-nanomagnetic\n bead enzyme-linked immunosorbent assay was employed to assess gene and protein expressions, as well as osteogenic biomarkers and interleukin-6 (IL-6) release, both in the presence or absence of a Piezo1 agonist/antagonist. Firstly, biophysical loading through mechanical strain was found to\n promote MSC osteogenic differentiation. Suppression of Piezo1 using GsMTx4 antagonist or transfection with Piezo1-siRNA effectively inhibited mechanical responses associated with osteogenic gene expressions and IL-6. Activation of Piezo1 by Yoda1 mimicked the effects induced by mechanical\n strain on osteogenic gene expressions and IL-6 release, which were associated with YAP activation, upregulation, and nuclear accumulation of β-catenin. In conclusion, these findings significantly enhance our understanding of MSC mechanotransduction and hold great promise for drug\n development to enhance skeletal mass.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of biomedical nanotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1166/jbn.2024.3730","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Physical stimulation plays a crucial role in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs). However, the mechanotransductive mechanisms remain uncleared. Recent studies have suggested that the Piezo1 channel is essential for transforming mechanical
signals. Therefore, we investigate the Piezo1-mediated mechanisms in mechanical strain-regulated MSC osteogenic differentiation and release of proinflammatory cytokines. The tensile strain was applied to rat MSCs cultured in a monolayer to induce mechanical strain. The immuno-nanomagnetic
bead enzyme-linked immunosorbent assay was employed to assess gene and protein expressions, as well as osteogenic biomarkers and interleukin-6 (IL-6) release, both in the presence or absence of a Piezo1 agonist/antagonist. Firstly, biophysical loading through mechanical strain was found to
promote MSC osteogenic differentiation. Suppression of Piezo1 using GsMTx4 antagonist or transfection with Piezo1-siRNA effectively inhibited mechanical responses associated with osteogenic gene expressions and IL-6. Activation of Piezo1 by Yoda1 mimicked the effects induced by mechanical
strain on osteogenic gene expressions and IL-6 release, which were associated with YAP activation, upregulation, and nuclear accumulation of β-catenin. In conclusion, these findings significantly enhance our understanding of MSC mechanotransduction and hold great promise for drug
development to enhance skeletal mass.