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Journal of Inflammation

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Open Access 01-12-2018 | Research

Transient receptor potential ankyrin 1 (trpa1) mediates il-1β-induced apoptosis in rat chondrocytes via calcium overload and mitochondrial dysfunction

Authors: Songjiang Yin, Li Zhang, Liang Ding, Zhengquan Huang, Bo Xu, XiaoChen Li, Peimin Wang, Jun Mao

Published in: Journal of Inflammation | Issue 1/2018

Abstract

Background

Chondrocyte apoptosis is a central feature in the progression of osteoarthritis (OA), and would be triggered by sustained elevation of intracellular calcium ion (Ca²⁺), also known as a cellular second messenger. Transient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel, and the activation of which causes an influx of cation ions, in particularly Ca²⁺, into the activated cells. Therefore, we investigate the potential role of TRPA1 in mediating Ca²⁺ influx to promote chondrocyte apoptosis in OA.

Methods

The expression of TRPA1 in interleukin (IL)-1β-treated rat chondrocytes was assessed by Polymerase chain reaction (PCR) and Western blot (WB), and the functionality of TRPA1 channel by Ca²⁺ influx measurements. Meanwhile, the chondrocyte apoptosis in IL-1β-treated cells was measured by TUNEL assay and flow cytometry. The measurement of mitochondrial membrane potential and apoptosis-associated proteins after inhibition of TRPA1 were also performed in IL-1β-treated rat chondrocytes.

Results

After being induced by IL-1β, the gene and protein expression of TRPA1 was increased in the dose-dependent manner. Meanwhile, Ca²⁺ influx mediated by TRPA1 in rat chondrocytes was also enhanced. Pharmacological inhibition of TRPA1 downregulated the apoptotic rate in IL-1β-treated rat chondrocytes. In addition, the membrane potential depolarization was improved and significantly increased expression of apoptosis-associated proteins also reduced by the TRPA1 antagonist.

Conclusions

We found the IL-1β caused the increased functional expression of TRPA1, the activation of which involved IL-1β-induced apoptosis in rat chondrocytes. The potential mechanism may be linked to the intracellular calcium overload mediated by TRPA1 and attendant mitochondrial dysfunction.

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Title: Transient receptor potential ankyrin 1 (trpa1) mediates il-1β-induced apoptosis in rat chondrocytes via calcium overload and mitochondrial dysfunction
Authors: Songjiang Yin
Li Zhang
Liang Ding
Zhengquan Huang
Bo Xu
XiaoChen Li
Peimin Wang
Jun Mao
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Inflammation / Issue 1/2018
Electronic ISSN: 1476-9255
DOI: https://doi.org/10.1186/s12950-018-0204-9

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Results

Conclusions

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