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Int J Biol Sci 2024; 20(7):2370-2387. doi:10.7150/ijbs.88534 This issue Cite

Research Paper

Dysfunction of STING Autophagy Degradation in Senescent Nucleus Pulposus Cells Accelerates Intervertebral Disc Degeneration

Zhiqian Chen*, Chen Chen*, Xiao Yang, Yifan Zhou, Xiankun Cao, Chen Han, Tangjun Zhou✉, Jie Zhao✉, An Qin✉

Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, P. R. China.
*These authors contributed equally to this work.

✉ Corresponding authors: E-mail: dr_qinancom, profzhaojiecom, zhoutangjuncom.

Citation:
Chen Z, Chen C, Yang X, Zhou Y, Cao X, Han C, Zhou T, Zhao J, Qin A. Dysfunction of STING Autophagy Degradation in Senescent Nucleus Pulposus Cells Accelerates Intervertebral Disc Degeneration. Int J Biol Sci 2024; 20(7):2370-2387. doi:10.7150/ijbs.88534. https://www.ijbs.com/v20p2370.htm
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Abstract

Graphic abstract

The pathogenesis of Intervertebral Disc Degeneration (IDD) is complex and multifactorial, with cellular senescence of nucleus pulposus (NP) cells and inflammation playing major roles in the progression of IDD. The stimulator of interferon genes (STING) axis is a key mediator of inflammation during infection, cellular stress, and tissue damage. Here, we present a progressive increase in STING in senescent NP cells with the degradation disorder. The STING degradation function in normal NP cells can prevent IDD. However, the dysfunction of STING degradation through autophagy causes the accumulation and high expression of STING in senescent NP cells as well as inflammation continuous activation together significantly promotes IDD. In senescent NP cells and intervertebral discs (IVDs), we found that STING autophagy degradation was significantly lower than that of normal NP cells and IVDs when STING was activated by 2'3'-cGAMP. Also, the above phenomenon was found in STINGgt/gt, cGAS-/- mice with models of age-induced, lumbar instability-induced IDD as well as found in the rat caudal IVD puncture models. Taken together, we suggested that the promotion of STING autophagy degradation in senescent NP Cells demonstrated a potential therapeutic modality for the treatment of IDD.

Keywords: STING Degradation, Autophagy, Intervertebral Disc Degeneration, Nucleus Pulposus Cells, Senescence.

Citation styles

APA
Chen, Z., Chen, C., Yang, X., Zhou, Y., Cao, X., Han, C., Zhou, T., Zhao, J., Qin, A. (2024). Dysfunction of STING Autophagy Degradation in Senescent Nucleus Pulposus Cells Accelerates Intervertebral Disc Degeneration. International Journal of Biological Sciences, 20(7), 2370-2387. https://doi.org/10.7150/ijbs.88534.

ACS
Chen, Z.; Chen, C.; Yang, X.; Zhou, Y.; Cao, X.; Han, C.; Zhou, T.; Zhao, J.; Qin, A. Dysfunction of STING Autophagy Degradation in Senescent Nucleus Pulposus Cells Accelerates Intervertebral Disc Degeneration. Int. J. Biol. Sci. 2024, 20 (7), 2370-2387. DOI: 10.7150/ijbs.88534.

NLM
Chen Z, Chen C, Yang X, Zhou Y, Cao X, Han C, Zhou T, Zhao J, Qin A. Dysfunction of STING Autophagy Degradation in Senescent Nucleus Pulposus Cells Accelerates Intervertebral Disc Degeneration. Int J Biol Sci 2024; 20(7):2370-2387. doi:10.7150/ijbs.88534. https://www.ijbs.com/v20p2370.htm

CSE
Chen Z, Chen C, Yang X, Zhou Y, Cao X, Han C, Zhou T, Zhao J, Qin A. 2024. Dysfunction of STING Autophagy Degradation in Senescent Nucleus Pulposus Cells Accelerates Intervertebral Disc Degeneration. Int J Biol Sci. 20(7):2370-2387.

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