TNF‐α‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCP
Abstract Regular quiescence and activation are important for the function of bone marrow mesenchymal stem cells (BMMSC), multipotent stem cells that are widely used in the clinic due to their capabilities in tissue repair and inflammatory disease treatment. TNF‐α is previously reported to regulate B...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202303388 |
| _version_ | 1827319088808984576 |
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| author | Zepeng Su Jinteng Li Jiajie Lin Zhikun Li Yunshu Che Zhaoqiang Zhang Guan Zheng Guiwen Ye Wenhui Yu Yipeng Zeng Peitao Xu Xiaojun Xu Zhongyu Xie Yanfeng Wu Huiyong Shen |
| author_facet | Zepeng Su Jinteng Li Jiajie Lin Zhikun Li Yunshu Che Zhaoqiang Zhang Guan Zheng Guiwen Ye Wenhui Yu Yipeng Zeng Peitao Xu Xiaojun Xu Zhongyu Xie Yanfeng Wu Huiyong Shen |
| author_sort | Zepeng Su |
| collection | DOAJ |
| description | Abstract Regular quiescence and activation are important for the function of bone marrow mesenchymal stem cells (BMMSC), multipotent stem cells that are widely used in the clinic due to their capabilities in tissue repair and inflammatory disease treatment. TNF‐α is previously reported to regulate BMMSC functions, including multilineage differentiation and immunoregulation. The present study demonstrates that TNF‐α impedes quiescence and promotes the activation of BMMSC in vitro and in vivo. Mechanistically, the TNF‐α‐induced expression of KAT2A promotes the succinylation of VCP at K658, which inhibits the interaction between VCP and MFN1 and thus inhibits mitophagy. Furthermore, activated BMMSC exhibits stronger fracture repair and immunoregulation functions in vivo. This study contributes to a better understanding of the mechanisms of BMMSC quiescence and activation and to improving the effectiveness of BMMSC in clinical applications. |
| first_indexed | 2024-04-25T00:13:51Z |
| format | Article |
| id | doaj.art-d37ba250bae5450390351ac4ce9f09ea |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-25T00:13:51Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-d37ba250bae5450390351ac4ce9f09ea2024-03-13T07:30:35ZengWileyAdvanced Science2198-38442024-03-011110n/an/a10.1002/advs.202303388TNF‐α‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCPZepeng Su0Jinteng Li1Jiajie Lin2Zhikun Li3Yunshu Che4Zhaoqiang Zhang5Guan Zheng6Guiwen Ye7Wenhui Yu8Yipeng Zeng9Peitao Xu10Xiaojun Xu11Zhongyu Xie12Yanfeng Wu13Huiyong Shen14Department of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaCenter for Biotherapy The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaDepartment of Orthopedics The Eighth Affiliated Hospital of Sun Yat‐Sen University Shenzhen 518000 ChinaAbstract Regular quiescence and activation are important for the function of bone marrow mesenchymal stem cells (BMMSC), multipotent stem cells that are widely used in the clinic due to their capabilities in tissue repair and inflammatory disease treatment. TNF‐α is previously reported to regulate BMMSC functions, including multilineage differentiation and immunoregulation. The present study demonstrates that TNF‐α impedes quiescence and promotes the activation of BMMSC in vitro and in vivo. Mechanistically, the TNF‐α‐induced expression of KAT2A promotes the succinylation of VCP at K658, which inhibits the interaction between VCP and MFN1 and thus inhibits mitophagy. Furthermore, activated BMMSC exhibits stronger fracture repair and immunoregulation functions in vivo. This study contributes to a better understanding of the mechanisms of BMMSC quiescence and activation and to improving the effectiveness of BMMSC in clinical applications.https://doi.org/10.1002/advs.202303388BMMSCmitophagyquiescencesuccinylationTNF‐α |
| spellingShingle | Zepeng Su Jinteng Li Jiajie Lin Zhikun Li Yunshu Che Zhaoqiang Zhang Guan Zheng Guiwen Ye Wenhui Yu Yipeng Zeng Peitao Xu Xiaojun Xu Zhongyu Xie Yanfeng Wu Huiyong Shen TNF‐α‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCP Advanced Science BMMSC mitophagy quiescence succinylation TNF‐α |
| title | TNF‐α‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCP |
| title_full | TNF‐α‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCP |
| title_fullStr | TNF‐α‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCP |
| title_full_unstemmed | TNF‐α‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCP |
| title_short | TNF‐α‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCP |
| title_sort | tnf α induced kat2a impedes bmmsc quiescence by mediating succinylation of the mitophagy related protein vcp |
| topic | BMMSC mitophagy quiescence succinylation TNF‐α |
| url | https://doi.org/10.1002/advs.202303388 |
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