Elucidating the mechanism of IL-1β-Mediated Piezo1 expression regulation of chondrocyte autophagy and apoptosis via the PI3K/AKT/mTOR signaling Pathway
Copyright © 2023 Elsevier Ltd. All rights reserved..
For the pathogenesis of osteoarthritis (OA), the classical view is that chondrocyte apoptosis is associated with and may cause age-related joint degeneration. Recent observations indicate that Piezo1, a mechanical stress channel expressed in articular cartilage, plays a crucial role in this process. We wanted to investigate whether other conditions activate the expression of Piezo1 in chondrocytes. Therefore, we simulated OA to investigate whether Piezo1 gene expression and channel function were affected by the inflammatory factor,interleukin-1β, and the role of Piezo1 in the regulation of autophagy and apoptosis of chondrocytes. After the primary culture of human chondrocytes, the primary chondrocytes were treated with different concentrations of IL-1β. It was found that IL-1β upregulated the expression of Piezo1 in human chondrocytes. After Piezo1 activation, we analyzed the expression of autophagy and apoptosis of chondrocytes and investigated whether the downstream PI3K/AKT/mTOR pathway mediated the autophagy and apoptosis of chondrocytes. IL-1β activates Piezo1 to inhibit chondrocyte autophagy and promote chondrocyte apoptosis partially, represented by up-regulation of related proteins c-caspase 3, Bax expression, and down-regulation of Bcl2, LC3, p62 expression. Piezo1-siRNA inverted this step partially. Inhibition of the PI3K/AKT/mTOR pathway reduces Piezo1 inhibition of chondrocyte autophagy and activation of chondrocyte apoptosis. Therefore, IL-1β-mediated Piezo1 inhibition of chondrocyte autophagy and promotion of chondrocyte apoptosis partially through the PI3K/AKT/mTOR pathway is considered a novel pathogenesis of osteoarthritis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:86 |
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| Enthalten in: |
Tissue & cell - 86(2024) vom: 21. Jan., Seite 102291 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Wanzhuo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.01.2024 Date Revised 27.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.tice.2023.102291 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a For the pathogenesis of osteoarthritis (OA), the classical view is that chondrocyte apoptosis is associated with and may cause age-related joint degeneration. Recent observations indicate that Piezo1, a mechanical stress channel expressed in articular cartilage, plays a crucial role in this process. We wanted to investigate whether other conditions activate the expression of Piezo1 in chondrocytes. Therefore, we simulated OA to investigate whether Piezo1 gene expression and channel function were affected by the inflammatory factor,interleukin-1β, and the role of Piezo1 in the regulation of autophagy and apoptosis of chondrocytes. After the primary culture of human chondrocytes, the primary chondrocytes were treated with different concentrations of IL-1β. It was found that IL-1β upregulated the expression of Piezo1 in human chondrocytes. After Piezo1 activation, we analyzed the expression of autophagy and apoptosis of chondrocytes and investigated whether the downstream PI3K/AKT/mTOR pathway mediated the autophagy and apoptosis of chondrocytes. IL-1β activates Piezo1 to inhibit chondrocyte autophagy and promote chondrocyte apoptosis partially, represented by up-regulation of related proteins c-caspase 3, Bax expression, and down-regulation of Bcl2, LC3, p62 expression. Piezo1-siRNA inverted this step partially. Inhibition of the PI3K/AKT/mTOR pathway reduces Piezo1 inhibition of chondrocyte autophagy and activation of chondrocyte apoptosis. Therefore, IL-1β-mediated Piezo1 inhibition of chondrocyte autophagy and promotion of chondrocyte apoptosis partially through the PI3K/AKT/mTOR pathway is considered a novel pathogenesis of osteoarthritis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a Chondrocytes | |
| 650 | 4 | |a IL-1β | |
| 650 | 4 | |a Osteoarthritis (OA) | |
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