WAC Facilitates Mitophagy‐mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination‐Dependent Degradation
Abstract Osteogenic differentiation of mesenchymal stem cells (MSCs) plays a pivotal role in the pathogenesis and treatment of bone‐related conditions such as osteoporosis and bone regeneration. While the WW domain‐containing coiled‐coil adaptor (WAC) protein is primarily associated with transcripti...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202404107 |
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| author | Shuai Fan Jinteng Li Guan Zheng Ziyue Ma Xiaoshuai Peng Zhongyu Xie Wenjie Liu Wenhui Yu Jiajie Lin Zepeng Su Peitao Xu Peng Wang Yanfeng Wu Huiyong Shen Guiwen Ye |
| author_facet | Shuai Fan Jinteng Li Guan Zheng Ziyue Ma Xiaoshuai Peng Zhongyu Xie Wenjie Liu Wenhui Yu Jiajie Lin Zepeng Su Peitao Xu Peng Wang Yanfeng Wu Huiyong Shen Guiwen Ye |
| author_sort | Shuai Fan |
| collection | DOAJ |
| description | Abstract Osteogenic differentiation of mesenchymal stem cells (MSCs) plays a pivotal role in the pathogenesis and treatment of bone‐related conditions such as osteoporosis and bone regeneration. While the WW domain‐containing coiled‐coil adaptor (WAC) protein is primarily associated with transcriptional regulation and autophagy, its involvement in MSC osteogenesis remains unclear. Here, the data reveal that the levels of WAC are diminished in both osteoporosis patients and osteoporosis mouse models. It plays a pivotal function in facilitating MSC osteogenesis and enhancing new bone formation both in vitro and in vivo. Mechanistically, WAC promotes MSC osteogenesis by protecting PINK1, a crucial initiator of mitophagy, from ubiquitination‐dependent degradation thereby activating mitophagy. Interestingly, WAC interacts with the TM domains of PINK1 and prevents the K137 site from ubiquitination modification. The study elucidates the mechanism by which WAC modulates MSC osteogenesis, binds to PINK1 to protect it from ubiquitination, and identifies potential therapeutic targets for osteoporosis and bone defect repair. |
| format | Article |
| id | doaj-art-731adf2a59e44f12b1b9749788b50078 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-731adf2a59e44f12b1b9749788b500782025-01-13T15:29:43ZengWileyAdvanced Science2198-38442025-01-01122n/an/a10.1002/advs.202404107WAC Facilitates Mitophagy‐mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination‐Dependent DegradationShuai Fan0Jinteng Li1Guan Zheng2Ziyue Ma3Xiaoshuai Peng4Zhongyu Xie5Wenjie Liu6Wenhui Yu7Jiajie Lin8Zepeng Su9Peitao Xu10Peng Wang11Yanfeng Wu12Huiyong Shen13Guiwen Ye14Department of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaCenter for Biotherapy The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaDepartment of Orthopedics The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518033 P. R. ChinaAbstract Osteogenic differentiation of mesenchymal stem cells (MSCs) plays a pivotal role in the pathogenesis and treatment of bone‐related conditions such as osteoporosis and bone regeneration. While the WW domain‐containing coiled‐coil adaptor (WAC) protein is primarily associated with transcriptional regulation and autophagy, its involvement in MSC osteogenesis remains unclear. Here, the data reveal that the levels of WAC are diminished in both osteoporosis patients and osteoporosis mouse models. It plays a pivotal function in facilitating MSC osteogenesis and enhancing new bone formation both in vitro and in vivo. Mechanistically, WAC promotes MSC osteogenesis by protecting PINK1, a crucial initiator of mitophagy, from ubiquitination‐dependent degradation thereby activating mitophagy. Interestingly, WAC interacts with the TM domains of PINK1 and prevents the K137 site from ubiquitination modification. The study elucidates the mechanism by which WAC modulates MSC osteogenesis, binds to PINK1 to protect it from ubiquitination, and identifies potential therapeutic targets for osteoporosis and bone defect repair.https://doi.org/10.1002/advs.202404107mesenchymal stem cellmitophagyosteogenesisPINK1WAC |
| spellingShingle | Shuai Fan Jinteng Li Guan Zheng Ziyue Ma Xiaoshuai Peng Zhongyu Xie Wenjie Liu Wenhui Yu Jiajie Lin Zepeng Su Peitao Xu Peng Wang Yanfeng Wu Huiyong Shen Guiwen Ye WAC Facilitates Mitophagy‐mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination‐Dependent Degradation Advanced Science mesenchymal stem cell mitophagy osteogenesis PINK1 WAC |
| title | WAC Facilitates Mitophagy‐mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination‐Dependent Degradation |
| title_full | WAC Facilitates Mitophagy‐mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination‐Dependent Degradation |
| title_fullStr | WAC Facilitates Mitophagy‐mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination‐Dependent Degradation |
| title_full_unstemmed | WAC Facilitates Mitophagy‐mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination‐Dependent Degradation |
| title_short | WAC Facilitates Mitophagy‐mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination‐Dependent Degradation |
| title_sort | wac facilitates mitophagy mediated msc osteogenesis and new bone formation via protecting pink1 from ubiquitination dependent degradation |
| topic | mesenchymal stem cell mitophagy osteogenesis PINK1 WAC |
| url | https://doi.org/10.1002/advs.202404107 |
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