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Nitric oxide-caused rabbit chondrocyte apoptosis is linked to cytoskeletal protein proteolysis anomaly through intracellular JNK and ERK signal pathways

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A Correction to this article was published on 03 August 2022

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Abstract

Backgrounds

Nitric oxide (NO) plays a key role in the pathological chondrocyte apoptosis of osteoarthritis (OA). Cytoskeletal proteins form cytoskeleton network to maintain normal chondrocyte structure and function. JNK and ERK pathways are the signal pathways involved in the cell apoptosis. The role of cytoskeletal proteins in cytoskeleton perturbation and cell apoptosis was investigated in this study.

Objectives

In vitro cell apoptosis was induced in rabbit articular chondrocytes by NO donor Sodium Nitroprusside (SNP). The JNK-specific inhibitor SP600125 and ERK-specific inhibitor PD98059 were employed to clarify the mechanism. The level of apoptosis was evaluated by TUNEL assay and Annexin V flow cytometry.

Results

SNP induced concentration-dependent apoptosis, which was further enhanced by PD98059 but reduced by SP600125. Furthermore, PD98059 significantly increased caspase-3 expression and activity respectively, whereas SP600125 reduced caspase-3 expression and activity. SP600125 increased the cytoskeletal protein mRNA and protein expression, while PD98059 decreased them.

Conclusion

Intracellular JNK/ERK pathways were involved in chondrocyte apoptosis induced by SNP through oppositely regulated effects on cytoskeletal proteins; ERK pathway protected cytoskeletal protein from dissolution via inhibition of caspase-3 activation, while JNK pathway promoted the dissolution via activation of caspase-3 activity.

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Acknowledgements

This work was funded by National Natural Science Foundation of China (No. 81673115 and 82073496), Huimin project of Ministry of science and technology of China (grant number 2012GS610101), Department of Health of Shaanxi Province (Project number: 2018D050), and International Cooperation Foundation of Shaanxi province (2020KW-057). CC was supported by Australian NHMRC and The University of Queensland.

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Author notes

  1. Qun Chen and Xibin Kao have contributed equally to this manuscript.

Authors and Affiliations

  1. Institute of Endemic Diseases, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi’an, Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi, People’s Republic of China

    Qun Chen & Jinghong Chen

  2. Institute for Hygiene of Ordnance Industry, Xi’an, 710061, Shaanxi, People’s Republic of China

    Xibin Kao

  3. Institute of Health Supervision, Beilin District, Xi’an, 710003, Shaanxi, People’s Republic of China

    Yan Gao

  4. Shandong Shenghua Electronic New Materials Co., Ltd., Yantai, Shandong, China

    Zhaoheng Dong

  5. Endocrinology, School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia

    Chen Chen

Authors
  1. Qun Chen
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  2. Xibin Kao
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Contributions

Chen Qun: conceptualization, validation, investigation, data curation, writing—original draft, funding acquisition. Kao Xibin: methodology, formal analysis, data curation, validation. Gao Yan: methodology, validation. Chen Jinghong: supervision. Dong Zhaoheng: project administration. Chen Chen: result interpretation & discussion, report writing, reviewing & editing.

Corresponding author

Correspondence to Qun Chen.

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Conflict of interest

Qun Chen declares that she has no conflict of interest. Xibin Kao declares that he has no conflict of interest. Yan Gao declares that she has no conflict of interest. Jinghong Chen declares that she has no conflict of interest. Zhaoheng Dong declares that he has no conflict of interest. Chen Chen declares that he has no conflict of interest.

Ethical approval

This research was approved by the Ethics Committee of Xi'an Jiaotong University Health Science Center (License number 2011058).

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The original online version of this article was revised: In this article Fig. 5 has been updated.

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Chen, Q., Kao, X., Gao, Y. et al. Nitric oxide-caused rabbit chondrocyte apoptosis is linked to cytoskeletal protein proteolysis anomaly through intracellular JNK and ERK signal pathways. Mol. Cell. Toxicol. 19, 71–79 (2023). https://doi.org/10.1007/s13273-022-00241-1

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  • DOI: https://doi.org/10.1007/s13273-022-00241-1

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