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SKI knockdown suppresses apoptosis and extracellular matrix degradation of nucleus pulposus cells via inhibition of the Wnt/β-catenin pathway and ameliorates disc degeneration

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Abstract

This study aimed to determine the effects of SKI on interleukin (IL)-1β-induced apoptosis of nucleus pulposus (NP) cells, intervertebral disc degeneration (IDD), and the Wnt signaling pathway. NP tissue specimens of different Pfirrmann grades (II–V) were collected from patients with different grades of IDD. Real-time polymerase chain reaction and western blotting were used to compare SKI mRNA and protein expression in NP tissues from patients. Using the IL-1β-induced IDD model, NP cells were infected with lentivirus-coated si-SKI to downregulate the expression of SKI and treated with LiCl to evaluate the involvement of the Wnt/β-catenin signaling pathway. Western blotting, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect NP cell apoptosis, extracellular matrix (ECM) metabolism, and related protein expression changes in the Wnt/β-catenin signaling pathway. To investigate the role of SKI in vivo, a rat IDD model was established by needle puncture of the intervertebral disc. Rats were injected with lentivirus-coated si-SKI and evaluated by magnetic resonance imaging (MRI), and hematoxylin and eosin (HE) and safranin O staining. SKI expression positively correlated with the severity of human IDD. In the IL-1β-induced NP cell degeneration model, SKI expression increased significantly and reached a peak at 24 h. SKI knockdown protected against IL-1β-induced NP cell apoptosis and ECM degradation. LiCl treatment reversed the protective effects of si-SKI on NP cells. Furthermore, lentivirus-coated si-SKI injection partially reversed the NP tissue damage in the IDD model in vivo. SKI knockdown reduced NP cell apoptosis and ECM degradation by inhibiting the Wnt/β-catenin signaling pathway, ultimately protecting against IDD. Therefore, SKI may be an effective target for IDD treatment.

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Acknowledgements

We thank Editage (www.editage.cn) for English language editing.

Funding

This work was co-funded by the National Natural Science Foundation of China (No. 31960175).

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Author notes

  1. Zuo-long Wu, Ya-jun Chen and Guang-zhi Zhang have contributed equally to this work and share first authorship

Authors and Affiliations

  1. Department of Orthopaedics, Second Hospital of Lanzhou University, Gansu, 730000, China

    Zuo-long Wu, Guang-zhi Zhang, Qi-qi Xie, Ke-ping Wang, Xin Yang, Tai-Cong Liu, Zhi-qiang Wang, Guang-hai Zhao & Hai-Hong Zhang

  2. Key Laboratory of Orthopaedics Disease of Gansu Province, Gansu, 730000, China

    Zuo-long Wu, Guang-zhi Zhang, Qi-qi Xie, Ke-ping Wang, Xin Yang, Tai-Cong Liu, Zhi-qiang Wang, Guang-hai Zhao & Hai-Hong Zhang

  3. Lanzhou University, Lanzhou, 730000, Gansu, China

    Zuo-long Wu, Ya-jun Chen, Guang-zhi Zhang, Qi-qi Xie, Ke-ping Wang, Xin Yang, Tai-Cong Liu, Zhi-qiang Wang, Guang-hai Zhao & Hai-Hong Zhang

  4. Lanzhou Maternal and Child Health Hospital, Lanzhou, 730000, Gansu, China

    Ya-jun Chen

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Contributions

Conceptualization: Z-LW, H-HZ, and Y-JC; methodology: G-ZZ; software: Q-QX; writing—original draft preparation: Z-LW and G-ZZ; writing—review and editing: Y-JC, Q-QX, and H-HZ; visualization: Y-JC; supervision: H-HZ; All authors have read and agreed to the published version of the manuscript.

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Correspondence to Hai-Hong Zhang.

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All experimental protocols were approved by the Ethics Committee of Lanzhou University Second Hospital, and written informed consent was obtained from each patient. The animal study was reviewed and approved by the Animal Use and Care Committee of Lanzhou University Second Hospital.

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Wu, Zl., Chen, Yj., Zhang, Gz. et al. SKI knockdown suppresses apoptosis and extracellular matrix degradation of nucleus pulposus cells via inhibition of the Wnt/β-catenin pathway and ameliorates disc degeneration. Apoptosis 27, 133–148 (2022). https://doi.org/10.1007/s10495-022-01707-2

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