期刊
OSTEOARTHRITIS AND CARTILAGE
卷 29, 期 8, 页码 1213-1224出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2021.04.017
关键词
Intervertebral disc degeneration; Senescence; Apoptosis; cGAS-STING
资金
- Zhejiang Provincial Natural Science Foundation of China [LGF20H060013, LGF21H060011]
- National Natural Science Foundation of China [81972094, 81770409]
- Zhejiang Provincial Project for Medical and Health Science and Technology [2020KY190]
STING upregulation in degenerated NP tissues promotes ECM degradation, apoptosis, and senescence, contributing to IVDD progression. Mechanistically, STING activates IRF3 pathway to exert its effects on IVDD development.
Objective: DNA damage induced by ROS is considered one of the main causes of nucleus pulposus (NP) cells degeneration during the progression of intervertebral disc degeneration (IVDD). cGAS-STING pathway acts as DNA-sensing mechanism for monitoring DNA damage. Recent studies have proved that cGAS-STING contributes to the development of various diseases by inducing inflammation, senescence, and apoptosis. This work explored the role of STING, the main effector of cGAS-STING signaling pathway, in NP degeneration. Method: Immunohistochemistry was conducted to measure STING protein levels in the nucleus pulposus tissues from human and puncture-induced IVDD rat models. TBHP induces degeneration of nucleus pulposus cells in vitro. For in vivo experiments, lv-NC or lv-STING were injected into the central intervertebral disc space. The degeneration level of IVDD was assessed by MRI, X-ray, HE, and Safranin O staining. Results: We found that the expression of STING was upregulated in human and rat degenerated NP tissue as well as in TBHP-treated NP cells. Overexpression of STING promoted the degradation of extracellular matrix; it also promoted apoptosis and senescence of TBHP-treated and untreated NP cells. Knock-down of STING significantly reversed these effects. Mechanistically, STING activated IRF3, whereas blockage of IRF3 attenuated STING-induced apoptosis, senescence and ECM degradation. In vivo experiments revealed that STING knock-down alleviated puncture-induced IVDD development. Conclusion: STING promotes IVDD progress via IRF3, while suppression of STING may be a promising treatment for IVDD. (c) 2021 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
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