Targeting STING attenuates ROS induced intervertebral disc degeneration
| Autor: | Shanshan Zeng, Yi-Han Wang, Xiaolei Zhang, Yan Lin, Ding-Chao Zhu, Yaosen Wu, Zhimin Miao, ligang Pan, Libo Wang, Xiangtao Zheng, Qiang Guo, Chongan Huang, Zhen Lin, Ze-Xin Chen, Jinwu Wang, Jia-Hao Lin |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Senescence Nucleus Pulposus DNA damage Biomedical Engineering Inflammation Apoptosis Intervertebral Disc Degeneration Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Rheumatology Downregulation and upregulation medicine Animals Humans Orthopedics and Sports Medicine Cellular Senescence 030203 arthritis & rheumatology Chemistry X-Rays Membrane Proteins Intervertebral disc Magnetic Resonance Imaging eye diseases Cell biology Extracellular Matrix Up-Regulation Sting 030104 developmental biology medicine.anatomical_structure Interferon Regulatory Factor-3 medicine.symptom Signal transduction Reactive Oxygen Species Signal Transduction |
| Zdroj: | Osteoarthritis and cartilage. 29(8) |
| ISSN: | 1522-9653 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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