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BAG3 protects chondrocytes against lumbar facet joint osteoarthritis by regulating autophagy and apoptosis

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Abstract

Bcl2-associated athanogene3 (BAG3) protein, mainly induced by stressful stimuli, has been confirmed to participate in apoptosis and autophagy. In recent studies, BAG3 has gradually become a key molecule in tumors. However, the role of BAG3 in the progression of lumbar facet joint osteoarthritis (FJOA) and whether it can regulate chondrocyte apoptosis and autophagy are still unknown. In both human and FJOA rat models, we observed an upregulation of BAG3 and apoptosis and autophagy-related proteins compared with healthy tissues. Then, we established the chondrocytes injury model in vitro by using IL-1β to stimulate human SW1353 cells. Western blot analysis data showed significant expression of BAG3, apoptosis, and autophagy-related proteins in SW1353 cells. Finally, by knocking down and overexpressing BAG3, we discovered possible anti-apoptotic and autophagy-promoted effects of BAG3 in FJOA through various experimental methods. This study demonstrated that BAG3 actively participates in regulating chondrocyte apoptosis and autophagy in FJOA and may be a highly interesting target for pharmacological interventions.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by Jiangsu Province Young Medical Key Talents Project of China (QNRC2016407), Nantong “14th Five-year plan” medical key talents project, Nantong City Science and Technology Project (MSZ18090, MS22015122) and The fifth phase of “226 High-level Talents Training Project” of Nantong City.

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Author notes

  1. Xin Lu and Jinlong Zhang contributed equally to this work

Authors and Affiliations

  1. Department of Orthopedic, Nantong Third People’s Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    Xin Lu, Jinlong Zhang, Pengfei Xue, Qinyu Wang, Xiangyu Wang, Yuyu Sun & Zhiming Cui

  2. Department of Spine Surgery, Nantong City No.1 People’s Hospital and Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    Xin Lu, Jinlong Zhang, Pengfei Xue, Qinyu Wang, Xiangyu Wang, Yuyu Sun & Zhiming Cui

  3. Nantong University, Nantong, 226001, Jiangsu, China

    Xin Lu, Jinlong Zhang, Pengfei Xue, Qinyu Wang, Xiangyu Wang, Yuyu Sun & Zhiming Cui

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  1. Xin Lu
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Contributions

Zhiming Cui contributed to the conception of the study; Xin Lu, Jinlong Zhang performed the experiment; Pengfei Xue, Qinyu Wang contributed significantly to analysis and manuscript preparation; Xin Lu, Guanhua Xu performed the data analyses and wrote the manuscript; Xin Lu, Zhiming Cui helped perform the analysis with constructive discussions. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Yuyu Sun or Zhiming Cui.

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Ethics approval

The collection of human facet joints was performed with the patients’ informed consent and was approved by the Human Ethics Committee of No. 2 People’s Hospital Affiliated to Nantong University. All animal experiments were approved by the Chinese National Committee to Use of Experimental Animals for Medical Purposes, Jiangsu Branch and the investigation is in accordance with the “Guidelines for the Care and Use of Laboratory Animals.”

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Written informed consent for participation was obtained from all participants.

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Written informed consent for publication was obtained from all participants.

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The authors declared that no competing interests.

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Key Points

1. BAG3 expression was elevated in FJOA patients and rats.

2. BAG3 was upregulated in IL-1β-stimulated SW1353 cells.

3. BAG3 could affect FJOA by regulating autophagy and apoptosis.

4. The physiological processes of BAG3 were jointly participated by HSP70.

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Lu, X., Zhang, J., Xue, P. et al. BAG3 protects chondrocytes against lumbar facet joint osteoarthritis by regulating autophagy and apoptosis. J Physiol Biochem 78, 427–437 (2022). https://doi.org/10.1007/s13105-021-00865-2

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  • DOI: https://doi.org/10.1007/s13105-021-00865-2

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