Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration
Bone defect repair remains a great challenge in the field of orthopedics. Human body essential trace element such as copper is essential for bone regeneration, but how to use it in bone defects and the underlying its mechanisms of promoting bone formation need to be further explored. In this study,...
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KeAi Communications Co., Ltd.
2025-04-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24005462 |
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| author | Ziji Ling Xiao Ge Chengyu Jin Zesheng Song Hang Zhang Yu Fu Kai Zheng Rongyao Xu Hongbing Jiang |
| author_facet | Ziji Ling Xiao Ge Chengyu Jin Zesheng Song Hang Zhang Yu Fu Kai Zheng Rongyao Xu Hongbing Jiang |
| author_sort | Ziji Ling |
| collection | DOAJ |
| description | Bone defect repair remains a great challenge in the field of orthopedics. Human body essential trace element such as copper is essential for bone regeneration, but how to use it in bone defects and the underlying its mechanisms of promoting bone formation need to be further explored. In this study, by doping copper into mesoporous bioactive glass nanoparticles (Cu-MBGNs), we unveil a previously unidentified role of copper in facilitating osteoblast mitophagy and mitochondrial dynamics, which enhance amorphous calcium phosphate (ACP) release and subsequent biomineralization, ultimately accelerating the process of bone regeneration. Specifically, by constructing conditional knockout mice lacking the autophagy gene Atg5 in osteogenic lineage cells, we first confirmed the role of Cu-MBGNs-promoted bone formation via mediating osteoblast autophagy pathway. Then, the in vitro studies revealed that Cu-MBGNs strengthened mitophagy by inducing ROS production and recruiting PINK1/Parkin, thereby facilitating the efficient release of ACP from mitochondria into matrix vesicles for biomineralization during bone regeneration. Moreover, we found that Cu-MBGNs promoted mitochondrion fission via activating dynamin related protein 1 (Drp1) to reinforce mitophagy pathway. Together, this study highlights the potential of Cu-MBGNs‐mediated mitophagy and biomineralization for augmenting bone regeneration, offering a promising avenue for the development of advanced bioactive materials in orthopedic applications. |
| format | Article |
| id | doaj-art-1bbd61383d844a71bff9b9bbd05d6b9a |
| institution | DOAJ |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-1bbd61383d844a71bff9b9bbd05d6b9a2025-08-20T03:11:54ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-04-014619521210.1016/j.bioactmat.2024.12.010Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regenerationZiji Ling0Xiao Ge1Chengyu Jin2Zesheng Song3Hang Zhang4Yu Fu5Kai Zheng6Rongyao Xu7Hongbing Jiang8Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, 210029, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, 210029, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, 210029, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, 210029, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, 210029, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, 210029, Nanjing, ChinaState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, 210029, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, 210029, Nanjing, China; Corresponding author. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China.Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, 210029, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, 210029, Nanjing, China; Corresponding author. State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, 210029, Nanjing, China.Bone defect repair remains a great challenge in the field of orthopedics. Human body essential trace element such as copper is essential for bone regeneration, but how to use it in bone defects and the underlying its mechanisms of promoting bone formation need to be further explored. In this study, by doping copper into mesoporous bioactive glass nanoparticles (Cu-MBGNs), we unveil a previously unidentified role of copper in facilitating osteoblast mitophagy and mitochondrial dynamics, which enhance amorphous calcium phosphate (ACP) release and subsequent biomineralization, ultimately accelerating the process of bone regeneration. Specifically, by constructing conditional knockout mice lacking the autophagy gene Atg5 in osteogenic lineage cells, we first confirmed the role of Cu-MBGNs-promoted bone formation via mediating osteoblast autophagy pathway. Then, the in vitro studies revealed that Cu-MBGNs strengthened mitophagy by inducing ROS production and recruiting PINK1/Parkin, thereby facilitating the efficient release of ACP from mitochondria into matrix vesicles for biomineralization during bone regeneration. Moreover, we found that Cu-MBGNs promoted mitochondrion fission via activating dynamin related protein 1 (Drp1) to reinforce mitophagy pathway. Together, this study highlights the potential of Cu-MBGNs‐mediated mitophagy and biomineralization for augmenting bone regeneration, offering a promising avenue for the development of advanced bioactive materials in orthopedic applications.http://www.sciencedirect.com/science/article/pii/S2452199X24005462CopperMesoporous bioactive glassMitophagyBiomineralizationBone regeneration |
| spellingShingle | Ziji Ling Xiao Ge Chengyu Jin Zesheng Song Hang Zhang Yu Fu Kai Zheng Rongyao Xu Hongbing Jiang Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration Bioactive Materials Copper Mesoporous bioactive glass Mitophagy Biomineralization Bone regeneration |
| title | Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration |
| title_full | Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration |
| title_fullStr | Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration |
| title_full_unstemmed | Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration |
| title_short | Copper doped bioactive glass promotes matrix vesicles-mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration |
| title_sort | copper doped bioactive glass promotes matrix vesicles mediated biomineralization via osteoblast mitophagy and mitochondrial dynamics during bone regeneration |
| topic | Copper Mesoporous bioactive glass Mitophagy Biomineralization Bone regeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24005462 |
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