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Silencing DDX3 Attenuates Interleukin-1β-Induced Intervertebral Disc Degeneration Through Inhibiting Pyroptosis

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Abstract

Intervertebral disc degeneration (IVDD) is a common disorder associated with chronic inflammation and cell death. In this study, an IVDD rat model was created through Interleukin-1β (IL-1β) injection. The degeneration of intervertebral disc tissues was assessed using magnetic resonance imaging (MRI), followed by hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining. RNA sequencing was performed to identify differentially expressed genes (DEGs) between the IVDD model and control rats. The expression levels of DEGs (DEAD-box polypeptide 3 (DDX3), lysine-specific demethylase 5D (KDM5D), interferon-induced gene-1 (IFIT1), ribosomal protein S10 (RPS10), tenomodulin (TNMD), and pentraxin 3 (PTX3)) were measured by real-time quantitative polymerase chain reaction (RT-qPCR). The regulatory effect of DDX3 on pyroptosis in IL-1β-treated nucleus pulpous (NP) cells was assessed after transfection with siRNA of DDX3. A total of 601 DEGs were identified from the IVDD model rat, and were abundant in extracellular matrix (ECM) organization, ECM-receptor interaction, and inflammatory pathways, including the PI3K-Akt, TNF, and AMPK signaling pathways. DDX3, KDM5D, and IFIT1 levels were notably elevated, whereas RPS10, TNMD, and PTX3 levels were decreased in the IL-1β-induced IVDD rat model. Moreover, silencing DDX3 promoted cell proliferation and abolished IL-1β-induced cell apoptosis and pyroptosis. This study revealed the role of DDX3 in IVDD pyroptosis, providing potential target for IVDD management.

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No datasets were generated or analysed during the current study.

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Authors and Affiliations

  1. Department of Orthopaedics, Ganzhou People’s Hospital, No.16 Meiguang Avenue, Ganzhou City, Jiangxi Province, 341000, China

    Hongfa Zhong, Mingheng Li, Haijian Wu, Hui Ying, Mingliang Zhong & Mouzhang Huang

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  1. Hongfa Zhong
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Contributions

All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Conceptualization, H.F.Z.; Methodology, M.H.L. and H.Y.; Investigation, H.J.W. M.L.Z. and M.Z.H.; Formal Analysis, H.F.Z. and M.H.L.; Resources, H.J.W. and M.L.Z.; Writing - Original Draft, H.F.Z. and M.H.L.; Writing - Review & Editing, H.J.W., H.Y., M.L.Z. and M.Z.H.; Supervision, H.F.Z. All authors reviewed and approved the manuscript.

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Correspondence to Hongfa Zhong.

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Zhong, H., Li, M., Wu, H. et al. Silencing DDX3 Attenuates Interleukin-1β-Induced Intervertebral Disc Degeneration Through Inhibiting Pyroptosis. Inflammation (2024). https://doi.org/10.1007/s10753-024-02042-1

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