The Mechanosensitive PIEZO1 Channel Contributes to the Reaction of RAW264.7 Macrophages to Mechanical Strain.

IF 4.4 3区 医学 Q2 CELL BIOLOGY
Mediators of Inflammation Pub Date : 2025-05-18 eCollection Date: 2025-01-01 DOI:10.1155/mi/9998838
Agnes Schröder, Hanna Engelhardt, Andressa Nogueira, Björn Clausen, Christian Kirschneck, Jonathan Jantsch, Peter Proff, Kathrin Renner, Eva Paddenberg-Schubert
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引用次数: 0

Abstract

The mechanosensitive channel 'piezo type mechanosensitive ion channel component 1' (PIEZO1) plays a regulatory role in the response of periodontal ligament fibroblasts (PDLFs) to the mechanical strain that occurs during orthodontic tooth movement. In addition to PDLFs, immune cells such as macrophages are also exposed to mechanical stimuli. Macrophages respond to mechanical strain with increased expression of inflammatory mediators. The role of PIEZO1 in this response remains elusive. To investigate the effect of PIEZO1 activation, RAW264.7 macrophages were stimulated with the PIEZO1 activator YODA1 without concurrent application of pressure. To further examine the specific role of PIEZO1 during mechanical strain, RAW264.7 macrophages were exposed to mechanical strain without and with simultaneous inhibition of PIEZO1 either by chemical inhibition (GsMTx4) or siRNA silencing. The expression of genes and proteins involved in orthodontic tooth movement was examined by quantitative PCR, western blot, and enzyme-linked immunosorbent assay (ELISA). Activation of PIEZO1 by YODA1 or mechanical strain increased the expression of inflammatory cytokines and osteoprotegerin (Opg), which is critically involved in bone remodeling processes. Conversely, inhibition of the PIEZO1 channel attenuates the effects of mechanical stress. In conclusion, our data demonstrate that the PIEZO1 channel is a major contributor to the response of macrophages to mechanical strain encountered during orthodontic tooth movement and affects the expression of inflammatory and bone remodeling factors.

机械敏感的PIEZO1通道参与RAW264.7巨噬细胞对机械应变的反应。
机械敏感通道“压电型机械敏感离子通道组分1”(PIEZO1)在牙周韧带成纤维细胞(PDLFs)对正畸牙齿运动过程中发生的机械应变的反应中起调节作用。除了PDLFs,免疫细胞如巨噬细胞也暴露于机械刺激下。巨噬细胞对机械应变的反应是增加炎症介质的表达。PIEZO1在这种反应中的作用仍然难以捉摸。为了研究PIEZO1激活的效果,在不同时施加压力的情况下,用PIEZO1激活剂YODA1刺激RAW264.7巨噬细胞。为了进一步研究PIEZO1在机械应变中的具体作用,我们将RAW264.7巨噬细胞暴露于机械应变中,同时通过化学抑制(GsMTx4)或siRNA沉默抑制PIEZO1。采用定量PCR、western blot和酶联免疫吸附试验(ELISA)检测正畸牙齿运动相关基因和蛋白的表达。YODA1或机械应变激活PIEZO1增加炎症细胞因子和骨保护素(Opg)的表达,这在骨重塑过程中至关重要。相反,抑制PIEZO1通道会减弱机械应力的影响。总之,我们的数据表明,在正畸牙齿运动过程中,PIEZO1通道是巨噬细胞对机械应变反应的主要因素,并影响炎症和骨重塑因子的表达。
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来源期刊
Mediators of Inflammation
Mediators of Inflammation 医学-免疫学
CiteScore
8.70
自引率
0.00%
发文量
202
审稿时长
4 months
期刊介绍: Mediators of Inflammation is a peer-reviewed, Open Access journal that publishes original research and review articles on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules.
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