Protective role of the alpha-1-antitrypsin in intervertebral disc degeneration
Abstract Background Intervertebral disc degeneration is a complex disease with high prevalence. It suggests that cell death, senescence, and extracellular matrix degradation are involved in the pathogenesis. Alpha-1 antitrypsin (AAT), a serine protease inhibitor, was previously correlated with infla...
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-021-02668-z |
| _version_ | 1798025986484207616 |
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| author | Weikun Liu Yanfu Wang |
| author_facet | Weikun Liu Yanfu Wang |
| author_sort | Weikun Liu |
| collection | DOAJ |
| description | Abstract Background Intervertebral disc degeneration is a complex disease with high prevalence. It suggests that cell death, senescence, and extracellular matrix degradation are involved in the pathogenesis. Alpha-1 antitrypsin (AAT), a serine protease inhibitor, was previously correlated with inflammation-related diseases. However, its function on intervertebral disc degeneration remains unclear. Methods A latex-enhanced immunoturbidimetric assay measured the serum level of AAT. Real-time polymerase chain reaction (RT-qPCR) and western blot were used to testify the expression of RNA and proteins related to cell apoptosis and the Wnt/β-catenin pathway. The animal model for intervertebral disc degeneration was built by disc puncture. The degeneration grades were analyzed by safranin o staining. Results We showed that alpha-1 antitrypsin could ameliorate intervertebral disc degeneration in vitro and in vivo. We also found that the serum alpha-1 antitrypsin level in Intervertebral disc degeneration patients is negative related to the severity of intervertebral disc degeneration. Moreover, alpha-1 antitrypsin was also showed to suppress tumor necrosis factor-alpha (TNF-α) induced WNT/β-catenin signaling pathway activation in human nucleus pulposus cells. Conclusions Our study provides evidence for AAT to serve as a potential therapeutic reagent for the treatment of intervertebral disc degeneration. |
| first_indexed | 2024-04-11T18:27:54Z |
| format | Article |
| id | doaj.art-a53873386eaf4afdbaed6dd344298644 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-11T18:27:54Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-a53873386eaf4afdbaed6dd3442986442022-12-22T04:09:33ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-08-011611810.1186/s13018-021-02668-zProtective role of the alpha-1-antitrypsin in intervertebral disc degenerationWeikun Liu0Yanfu Wang1Department of Orthopedics, People’s Hospital of Dongxihu DistrictDepartment of Rehabilitation Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Intervertebral disc degeneration is a complex disease with high prevalence. It suggests that cell death, senescence, and extracellular matrix degradation are involved in the pathogenesis. Alpha-1 antitrypsin (AAT), a serine protease inhibitor, was previously correlated with inflammation-related diseases. However, its function on intervertebral disc degeneration remains unclear. Methods A latex-enhanced immunoturbidimetric assay measured the serum level of AAT. Real-time polymerase chain reaction (RT-qPCR) and western blot were used to testify the expression of RNA and proteins related to cell apoptosis and the Wnt/β-catenin pathway. The animal model for intervertebral disc degeneration was built by disc puncture. The degeneration grades were analyzed by safranin o staining. Results We showed that alpha-1 antitrypsin could ameliorate intervertebral disc degeneration in vitro and in vivo. We also found that the serum alpha-1 antitrypsin level in Intervertebral disc degeneration patients is negative related to the severity of intervertebral disc degeneration. Moreover, alpha-1 antitrypsin was also showed to suppress tumor necrosis factor-alpha (TNF-α) induced WNT/β-catenin signaling pathway activation in human nucleus pulposus cells. Conclusions Our study provides evidence for AAT to serve as a potential therapeutic reagent for the treatment of intervertebral disc degeneration.https://doi.org/10.1186/s13018-021-02668-zIntervertebral disc degenerationAlpha-1 antitrypsinApoptosisExtracellular matrix degradationWNT/β-catenin signaling |
| spellingShingle | Weikun Liu Yanfu Wang Protective role of the alpha-1-antitrypsin in intervertebral disc degeneration Journal of Orthopaedic Surgery and Research Intervertebral disc degeneration Alpha-1 antitrypsin Apoptosis Extracellular matrix degradation WNT/β-catenin signaling |
| title | Protective role of the alpha-1-antitrypsin in intervertebral disc degeneration |
| title_full | Protective role of the alpha-1-antitrypsin in intervertebral disc degeneration |
| title_fullStr | Protective role of the alpha-1-antitrypsin in intervertebral disc degeneration |
| title_full_unstemmed | Protective role of the alpha-1-antitrypsin in intervertebral disc degeneration |
| title_short | Protective role of the alpha-1-antitrypsin in intervertebral disc degeneration |
| title_sort | protective role of the alpha 1 antitrypsin in intervertebral disc degeneration |
| topic | Intervertebral disc degeneration Alpha-1 antitrypsin Apoptosis Extracellular matrix degradation WNT/β-catenin signaling |
| url | https://doi.org/10.1186/s13018-021-02668-z |
| work_keys_str_mv | AT weikunliu protectiveroleofthealpha1antitrypsininintervertebraldiscdegeneration AT yanfuwang protectiveroleofthealpha1antitrypsininintervertebraldiscdegeneration |