TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo
Abstract Background Intervertebral disc degeneration (IDD) is one of the most common disorders related to the spine. Inflammation, apoptosis and extracellular matrix (ECM) degradation contribute to disc degeneration in nucleus pulposus cells (NPCs). This study focused on the role and mechanism of th...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-023-03028-4 |
| _version_ | 1797863976124547072 |
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| author | Kun Wang Dengbo Yao Yuxi Li Ming Li Weike Zeng Zhuangyao Liao Engming Chen Shixin Lu Kaihui Su Zhen Che Yuwei Liang Peng Wang Lin Huang |
| author_facet | Kun Wang Dengbo Yao Yuxi Li Ming Li Weike Zeng Zhuangyao Liao Engming Chen Shixin Lu Kaihui Su Zhen Che Yuwei Liang Peng Wang Lin Huang |
| author_sort | Kun Wang |
| collection | DOAJ |
| description | Abstract Background Intervertebral disc degeneration (IDD) is one of the most common disorders related to the spine. Inflammation, apoptosis and extracellular matrix (ECM) degradation contribute to disc degeneration in nucleus pulposus cells (NPCs). This study focused on the role and mechanism of the p38 inhibitor TAK-715 in intervertebral disc degeneration. Methods NPCs were treated with IL-1β to mimic apoptosis, followed by the addition of TAK-715. It was determined that apoptosis, inflammatory mediators (COX-2), inflammatory cytokines (HMGB1), and ECM components (collagen II, MMP9, ADAMTS5, and MMP3) existed in NPCs. In addition, the p38MAPK signaling pathways were examined. The role of TAK-715 in vivo was determined by acupuncture-induced intervertebral disc degeneration. Following an intradiscal injection of TAK-715, MRI and a histopathological analysis were conducted to assess the degree of degeneration. Results IL-1β-induced apoptosis was alleviated by TAK-715 in vitro, and antiapoptotic proteins were upregulated. Furthermore, TAK-715 blocked IL-1β-induced inflammatory mediator production (COX-2) and inflammatory cytokine production (HMGB1) and degraded the ECM (collagen II, MMP9, ADAMTS5, and MMP3). By inhibiting the phosphorylation of p38, TAK-715 exerted its effects. In a rat tail model, TAK-715 ameliorates puncture-induced disc degeneration based on MRI and histopathology evaluations. Conclusion TAK-715 attenuated intervertebral disc degeneration in vitro and in vivo, suggesting that it might be an effective treatment for IDD. |
| first_indexed | 2024-04-09T22:44:09Z |
| format | Article |
| id | doaj.art-c606c901c271427a8842837247cd1b41 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-09T22:44:09Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-c606c901c271427a8842837247cd1b412023-03-22T11:58:50ZengBMCArthritis Research & Therapy1478-63622023-03-0125111310.1186/s13075-023-03028-4TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivoKun Wang0Dengbo Yao1Yuxi Li2Ming Li3Weike Zeng4Zhuangyao Liao5Engming Chen6Shixin Lu7Kaihui Su8Zhen Che9Yuwei Liang10Peng Wang11Lin Huang12Department of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Eighth Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityAbstract Background Intervertebral disc degeneration (IDD) is one of the most common disorders related to the spine. Inflammation, apoptosis and extracellular matrix (ECM) degradation contribute to disc degeneration in nucleus pulposus cells (NPCs). This study focused on the role and mechanism of the p38 inhibitor TAK-715 in intervertebral disc degeneration. Methods NPCs were treated with IL-1β to mimic apoptosis, followed by the addition of TAK-715. It was determined that apoptosis, inflammatory mediators (COX-2), inflammatory cytokines (HMGB1), and ECM components (collagen II, MMP9, ADAMTS5, and MMP3) existed in NPCs. In addition, the p38MAPK signaling pathways were examined. The role of TAK-715 in vivo was determined by acupuncture-induced intervertebral disc degeneration. Following an intradiscal injection of TAK-715, MRI and a histopathological analysis were conducted to assess the degree of degeneration. Results IL-1β-induced apoptosis was alleviated by TAK-715 in vitro, and antiapoptotic proteins were upregulated. Furthermore, TAK-715 blocked IL-1β-induced inflammatory mediator production (COX-2) and inflammatory cytokine production (HMGB1) and degraded the ECM (collagen II, MMP9, ADAMTS5, and MMP3). By inhibiting the phosphorylation of p38, TAK-715 exerted its effects. In a rat tail model, TAK-715 ameliorates puncture-induced disc degeneration based on MRI and histopathology evaluations. Conclusion TAK-715 attenuated intervertebral disc degeneration in vitro and in vivo, suggesting that it might be an effective treatment for IDD.https://doi.org/10.1186/s13075-023-03028-4TAK-715Intervertebral disc degenerationIDDInflammationApoptosisp38MAPK |
| spellingShingle | Kun Wang Dengbo Yao Yuxi Li Ming Li Weike Zeng Zhuangyao Liao Engming Chen Shixin Lu Kaihui Su Zhen Che Yuwei Liang Peng Wang Lin Huang TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo Arthritis Research & Therapy TAK-715 Intervertebral disc degeneration IDD Inflammation Apoptosis p38MAPK |
| title | TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo |
| title_full | TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo |
| title_fullStr | TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo |
| title_full_unstemmed | TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo |
| title_short | TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo |
| title_sort | tak 715 alleviated il 1β induced apoptosis and ecm degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo |
| topic | TAK-715 Intervertebral disc degeneration IDD Inflammation Apoptosis p38MAPK |
| url | https://doi.org/10.1186/s13075-023-03028-4 |
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