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Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin

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 compressi...

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Autores principales: Xu, Haoran, Wei, Kang, Tu, Jingyao, Chen, Yangmengfan, He, Yi, Ding, Yifan, Xu, Huanhuan, Bao, Xinyu, Xie, Hui, Fang, Huang, Wang, Huan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634256/
https://www.ncbi.nlm.nih.gov/pubmed/34869327
http://dx.doi.org/10.3389/fcell.2021.741046
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author Xu, Haoran
Wei, Kang
Tu, Jingyao
Chen, Yangmengfan
He, Yi
Ding, Yifan
Xu, Huanhuan
Bao, Xinyu
Xie, Hui
Fang, Huang
Wang, Huan
author_facet Xu, Haoran
Wei, Kang
Tu, Jingyao
Chen, Yangmengfan
He, Yi
Ding, Yifan
Xu, Huanhuan
Bao, Xinyu
Xie, Hui
Fang, Huang
Wang, Huan
author_sort Xu, Haoran
collection PubMed
description 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.
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spelling pubmed-86342562021-12-02 Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin Xu, Haoran Wei, Kang Tu, Jingyao Chen, Yangmengfan He, Yi Ding, Yifan Xu, Huanhuan Bao, Xinyu Xie, Hui Fang, Huang Wang, Huan Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-11-15 /pmc/articles/PMC8634256/ /pubmed/34869327 http://dx.doi.org/10.3389/fcell.2021.741046 Text en Copyright © 2021 Xu, Wei, Tu, Chen, He, Ding, Xu, Bao, Xie, Fang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Xu, Haoran
Wei, Kang
Tu, Jingyao
Chen, Yangmengfan
He, Yi
Ding, Yifan
Xu, Huanhuan
Bao, Xinyu
Xie, Hui
Fang, Huang
Wang, Huan
Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title_full Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title_fullStr Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title_full_unstemmed Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title_short Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin
title_sort reducing inflammation and vascular invasion in intervertebral disc degeneration via cystathionine-γ-lyase inhibitory effect on e-selectin
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634256/
https://www.ncbi.nlm.nih.gov/pubmed/34869327
http://dx.doi.org/10.3389/fcell.2021.741046
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