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Knockdown of TRAF6 inhibits chondrocytes apoptosis and inflammation by suppressing the NF-κB pathway in lumbar facet joint osteoarthritis

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Abstract

Tumor necrosis factor receptor-associated factor 6 (TRAF6), a regulator of NF-κB signaling, has been discovered recently to be probably related to osteoarthritis, while the function of TRAF6 in lumbar facet joint osteoarthritis(FJOA)still remains unknown. The aim of this study was to probe the specific function of TRAF6 in chondrocytes and its connection with the pathophysiology of FJOA. We found upregulation of TRAF6 in FJOA cartilage by western blot analysis. In vitro, we stimulated immortalized human chondrocytes by LPS to establish the cells apoptosis model. Western blot analysis demonstrated that levels of TRAF6 and cleaved caspase-3/8 in the chondrocyte injury model increased significantly. Knockdown of TRAF6 suppressed the expression of matrix metallopeptidase-13 (MMP-13) and interleukin-6 (IL-6) induced by LPS, and alleviated cell apoptosis. Meanwhile, western blot and immunofluorescent staining demonstrated that IκBα degradation and p65 nuclear transportation were also inhibited, revealing that knockdown of TRAF6 suppressed activation of the NF-κB pathway in LPS-induced chondrocytes apoptosis model. Collectively, our findings suggest that TRAF6 plays a crucial role in FJOA development by regulating NF-κB signaling pathway. Knockdown of TRAF6 may supply a potential therapeutic strategy for FJOA.

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Acknowledgements

This work was supported by Clinical Medicine Project of Nantong University (2019JQ004), Nantong 226 High-level Talents Project (2018 III-341), Jiangsu Province Young Medical Key Talents Project of China (QNRC2016407), Youth Project of Nantong City Health and Family Planning Commission (QA2020007).

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  1. Jiawei Jiang, Jinlong Zhang and Chunshuai Wu have contributed equally to the work.

Authors and Affiliations

  1. Department of Spine Surgery, Affiliated Hospital 2 of Nantong University, Nantong, 226001, Jiangsu, China

    Jiawei Jiang, Jinlong Zhang, Chunshuai Wu, Chu Chen, Guofeng Bao, Guanhua Xu, Pengfei Xue, Yong Zhou & Zhiming Cui

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

    Yuyu Sun

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  1. Jiawei Jiang
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Jiang, J., Zhang, J., Wu, C. et al. Knockdown of TRAF6 inhibits chondrocytes apoptosis and inflammation by suppressing the NF-κB pathway in lumbar facet joint osteoarthritis. Mol Cell Biochem 476, 1929–1938 (2021). https://doi.org/10.1007/s11010-021-04048-x

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