MFG-E8 alleviates intervertebral disc degeneration by suppressing pyroptosis and extracellular matrix degradation in nucleus pulposus cells via Nrf2/TXNIP/NLRP3 axis
Abstract Intervertebral disc degeneration (IVDD) is a chronic age-related degenerative disease accompanied by complex pathophysiological mechanisms. Increasing evidence indicates that NLRP3 inflammasome mediated pyroptosis of nucleus pulposus (NP) cells displays an important role in the pathological...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01002-8 |
| _version_ | 1828767155265470464 |
|---|---|
| author | Haiwei Ma Chenglong Xie Zhengtai Chen Gaolu He Zihan Dai Hanchen Cai Haojie Zhang Hongwei Lu Hongqiang Wu Xinli Hu Kailiang Zhou Gang Zheng Huazi Xu Cong Xu |
| author_facet | Haiwei Ma Chenglong Xie Zhengtai Chen Gaolu He Zihan Dai Hanchen Cai Haojie Zhang Hongwei Lu Hongqiang Wu Xinli Hu Kailiang Zhou Gang Zheng Huazi Xu Cong Xu |
| author_sort | Haiwei Ma |
| collection | DOAJ |
| description | Abstract Intervertebral disc degeneration (IVDD) is a chronic age-related degenerative disease accompanied by complex pathophysiological mechanisms. Increasing evidence indicates that NLRP3 inflammasome mediated pyroptosis of nucleus pulposus (NP) cells displays an important role in the pathological progression of IVDD. Milk fat globule-EGF factor-8 (MFG-E8) is an endogenously secreted glycoprotein with beneficial effects of anti-inflammatory, antioxidant, and modulation of NLRP3 inflammasome. However, the effect of MFG-E8 on IVDD remains unclear. In this study, our purpose is to clarify the expression changes of MFG-E8 in the IVDD process and explore the role and mechanism of MFG-E8. We found that MFG-E8’s expression was reduced in degraded nucleus pulposus tissues of humans and rats as well as hydrogen peroxide (H2O2)-treated NP cells. Exogenous supplementation of MFG-E8 could rescue H2O2-induced oxidative stress, mitochondrial dysfunction, and NLRP3 inflammasome activation and protect NP cells from pyroptosis and extracellular matrix (ECM) degradation. Mechanistically, Nrf2/TXNIP/NLRP3 axis plays a crucial role in MFG-E8-mediated suppression of the above-pathological events. In vivo, we established a rat intervertebral disc acupuncture model and found that MFG-E8 administration effectively alleviated IVDD development by imageological and histomorphological evaluation. Overall, our findings revealed the internal mechanisms underlying MFG-E8 regulation in NP cells and its intrinsic value for IVDD therapy. |
| first_indexed | 2024-12-11T07:20:39Z |
| format | Article |
| id | doaj.art-0be47c42b98b4b17bc6fb31c9710fc62 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-11T07:20:39Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-0be47c42b98b4b17bc6fb31c9710fc622022-12-22T01:16:05ZengNature Publishing GroupCell Death Discovery2058-77162022-04-018111510.1038/s41420-022-01002-8MFG-E8 alleviates intervertebral disc degeneration by suppressing pyroptosis and extracellular matrix degradation in nucleus pulposus cells via Nrf2/TXNIP/NLRP3 axisHaiwei Ma0Chenglong Xie1Zhengtai Chen2Gaolu He3Zihan Dai4Hanchen Cai5Haojie Zhang6Hongwei Lu7Hongqiang Wu8Xinli Hu9Kailiang Zhou10Gang Zheng11Huazi Xu12Cong Xu13Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversitySchool of Second Clinical Medical, Wenzhou Medical UniversitySchool of Second Clinical Medical, Wenzhou Medical UniversitySchool of Second Clinical Medical, Wenzhou Medical UniversityDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityAbstract Intervertebral disc degeneration (IVDD) is a chronic age-related degenerative disease accompanied by complex pathophysiological mechanisms. Increasing evidence indicates that NLRP3 inflammasome mediated pyroptosis of nucleus pulposus (NP) cells displays an important role in the pathological progression of IVDD. Milk fat globule-EGF factor-8 (MFG-E8) is an endogenously secreted glycoprotein with beneficial effects of anti-inflammatory, antioxidant, and modulation of NLRP3 inflammasome. However, the effect of MFG-E8 on IVDD remains unclear. In this study, our purpose is to clarify the expression changes of MFG-E8 in the IVDD process and explore the role and mechanism of MFG-E8. We found that MFG-E8’s expression was reduced in degraded nucleus pulposus tissues of humans and rats as well as hydrogen peroxide (H2O2)-treated NP cells. Exogenous supplementation of MFG-E8 could rescue H2O2-induced oxidative stress, mitochondrial dysfunction, and NLRP3 inflammasome activation and protect NP cells from pyroptosis and extracellular matrix (ECM) degradation. Mechanistically, Nrf2/TXNIP/NLRP3 axis plays a crucial role in MFG-E8-mediated suppression of the above-pathological events. In vivo, we established a rat intervertebral disc acupuncture model and found that MFG-E8 administration effectively alleviated IVDD development by imageological and histomorphological evaluation. Overall, our findings revealed the internal mechanisms underlying MFG-E8 regulation in NP cells and its intrinsic value for IVDD therapy.https://doi.org/10.1038/s41420-022-01002-8 |
| spellingShingle | Haiwei Ma Chenglong Xie Zhengtai Chen Gaolu He Zihan Dai Hanchen Cai Haojie Zhang Hongwei Lu Hongqiang Wu Xinli Hu Kailiang Zhou Gang Zheng Huazi Xu Cong Xu MFG-E8 alleviates intervertebral disc degeneration by suppressing pyroptosis and extracellular matrix degradation in nucleus pulposus cells via Nrf2/TXNIP/NLRP3 axis Cell Death Discovery |
| title | MFG-E8 alleviates intervertebral disc degeneration by suppressing pyroptosis and extracellular matrix degradation in nucleus pulposus cells via Nrf2/TXNIP/NLRP3 axis |
| title_full | MFG-E8 alleviates intervertebral disc degeneration by suppressing pyroptosis and extracellular matrix degradation in nucleus pulposus cells via Nrf2/TXNIP/NLRP3 axis |
| title_fullStr | MFG-E8 alleviates intervertebral disc degeneration by suppressing pyroptosis and extracellular matrix degradation in nucleus pulposus cells via Nrf2/TXNIP/NLRP3 axis |
| title_full_unstemmed | MFG-E8 alleviates intervertebral disc degeneration by suppressing pyroptosis and extracellular matrix degradation in nucleus pulposus cells via Nrf2/TXNIP/NLRP3 axis |
| title_short | MFG-E8 alleviates intervertebral disc degeneration by suppressing pyroptosis and extracellular matrix degradation in nucleus pulposus cells via Nrf2/TXNIP/NLRP3 axis |
| title_sort | mfg e8 alleviates intervertebral disc degeneration by suppressing pyroptosis and extracellular matrix degradation in nucleus pulposus cells via nrf2 txnip nlrp3 axis |
| url | https://doi.org/10.1038/s41420-022-01002-8 |
| work_keys_str_mv | AT haiweima mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT chenglongxie mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT zhengtaichen mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT gaoluhe mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT zihandai mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT hanchencai mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT haojiezhang mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT hongweilu mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT hongqiangwu mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT xinlihu mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT kailiangzhou mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT gangzheng mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT huazixu mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis AT congxu mfge8alleviatesintervertebraldiscdegenerationbysuppressingpyroptosisandextracellularmatrixdegradationinnucleuspulposuscellsvianrf2txnipnlrp3axis |