Abstract
The incidence of degenerative spinal diseases, such as cervical spondylosis and thoracic and lumbar disc herniation, is increasing. These health problems have adversely affected human life and work. Surgical intervention is effective when intervertebral disc degeneration (IDD) causes nerve compression and/or severely limits daily activity. Early IDD patients generally do not require surgery. However, there is no effective method of impeding IDD progression. Thus, novel approaches to alleviating IDD deterioration are urgently required. Cystathionine-γ-lyase (CSE) and E-selectin (CD62E) are vital factors regulating vascular function and inflammation. However, their effects on IDD and vascular invasion in intervertebral discs (IVDs) are pending further exploration. Here, bioinformatics and human nucleus pulposus (NP) tissues analyses revealed that CSE was significantly downregulated and CD62E was upregulated in the NP tissues of IDD patients. We demonstrated that CSE overexpression, CD62E downregulation, and NF-κB (P65) inhibition mitigate inflammation and recover metabolic function in NP cells. Similarly, CSE attenuated vascular invasion induced by inflammatory irritation. Using a rat IDD model, we showed that CSE improved degeneration, inflammation, and microvascular invasion in NP tissue, whereas CD62E had the opposite effect. Taken together, our results indicated that the CSE/CD62E pathway could effectively improve the inflammatory environment and vascular invasion in IVD. Hence, the findings of this study propose a promising and valuable strategy for the treatment of patients with early IDD as well as postoperative adjuvant therapy in patients with severe IDD.
Highlights
Degenerative spinal diseases are associated with a series of chronic and progressive symptoms and can have a tremendous impact on the quality of human life (Khan et al, 2017; Molladavoodi et al, 2020; Yang et al, 2020)
To establish the optimal conditions necessary to induce intervertebral disc degeneration (IDD) models in vitro, rat nucleus pulposus (NP) cells were subjected to various IL-1β concentrations and exposure times
The total CSE and CD62E protein levels were significantly altered after 24 h of 5 ng/mL IL-1β treatment (Figures 1G–L)
Summary
Degenerative spinal diseases are associated with a series of chronic and progressive symptoms and can have a tremendous impact on the quality of human life (Khan et al, 2017; Molladavoodi et al, 2020; Yang et al, 2020). The incidence and early onset of degenerative spinal disease are increasing because of a growing aging population and an unhealthy lifestyle, respectively (Salminen et al, 1999; Karademir et al, 2017). Intervertebral disc degeneration (IDD) causes low back and leg pain and may compress spinal nerves in severe cases. Conservative treatments must be administered to alleviate certain clinical symptoms. A few studies reported that conservative treatments alone cannot attenuate the inflammatory environment or recover normal functioning of the nucleus pulposus (NP) in degenerating intervertebral discs (IVDs).
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