Author:
Shi Sheng,Kang Xing-Jian,Zhou Zhi,He Zhi-Min,Zheng Shuang,He Shi-Sheng
Abstract
Abstract
Background
Mechanical stress plays a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). The mechanosensitive Piezo1 ion channel can sense the changes in mechanical stress and convert the mechanical signals into chemical signals. This study aims to investigate the effect of Piezo1 on the mechanical stress-induced IVDD and explore the possible mechanism.
Methods
The expression of Piezo1 and collagen II in immunohistochemical staining, cervical curvature, and the stiffness of nucleus pulpous (NP) were performed in normal and degenerated human intervertebral discs. In the experiment, high-intensity compression was applied to mimic the mechanical environment of IVDD. The cell viability, matrix macromolecules, and pro-inflammatory cytokines were examined to investigate the effect of Piezo1 on mechanical stress-treated NP cells. Additionally, autophagy condition of NP cells was detected within high-intensity compression and/or the inhibitor of Piezo1, GsMTx4.
Results
The up-expression of Piezo1, down-expression of Col II, elevated stiffness of NP, and poor kyphosis were observed in degenerated human intervertebral discs. High-intensity stress significantly decreased cell viability and the synthesis of extracellular matrix but increased the expression of senescence-associated proteins (p53 and p16) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) by mitochondrial dysfunction and suppression of autophagy. However, GsMTx4 can partly attenuate these effects.
Conclusion
Piezo1 upregulation under excessive mechanical stress promotes the apoptosis, senescence, and pro-inflammatory cytokines of NP and leads to the loss of extracellular matrix by mitochondrial dysfunction and the suppression of autophagy; on the other hand, the inhibition of Piezo1 can partly alleviate these effects.
Funder
Postdoctoral Research Foundation of China
Science and Technology Commission of Shanghai Municipality
Publisher
Springer Science and Business Media LLC
Cited by
21 articles.
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