Targeting STING attenuates ROS induced intervertebral disc degeneration

Summary

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.