Youthful Stem Cell Microenvironments: Rejuvenating Aged Bone Repair Through Mitochondrial Homeostasis Remodeling
Abstract Extracellular matrix (ECM) derived from mesenchymal stem cells regulates antioxidant properties and bone metabolism by providing a favorable extracellular microenvironment. However, its functional role and molecular mechanism in mitochondrial function regulation and aged bone regeneration r...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409644 |
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| author | Xinfeng Zhou Xin Tian Jianan Chen Yantong Li Nanning Lv Hao Liu Tao Liu Huilin Yang Xi Chen Yong Xu Fan He |
| author_facet | Xinfeng Zhou Xin Tian Jianan Chen Yantong Li Nanning Lv Hao Liu Tao Liu Huilin Yang Xi Chen Yong Xu Fan He |
| author_sort | Xinfeng Zhou |
| collection | DOAJ |
| description | Abstract Extracellular matrix (ECM) derived from mesenchymal stem cells regulates antioxidant properties and bone metabolism by providing a favorable extracellular microenvironment. However, its functional role and molecular mechanism in mitochondrial function regulation and aged bone regeneration remain insufficiently elucidated. This proteomic analysis has revealed a greater abundance of proteins supporting mitochondrial function in the young ECM (Y‐ECM) secreted by young bone marrow‐derived mesenchymal stem cells (BMMSCs) compared to the aged ECM (A‐ECM). Further studies demonstrate that Y‐ECM significantly rejuvenates mitochondrial energy metabolism in adult BMMSCs (A‐BMMSCs) through the promotion of mitochondrial respiratory functions and amelioration of oxidative stress. A‐BMMSCs cultured on Y‐ECM exhibited enhanced multi‐lineage differentiation potentials in vitro and ectopic bone formation in vivo. Mechanistically, silencing of silent information regulator type 3 (SIRT3) gene abolished the protective impact of Y‐ECM on A‐BMMSCs. Notably, a novel composite biomaterial combining hyaluronic acid methacrylate hydrogel microspheres with Y‐ECM is developed, which yielded substantial improvements in the healing of bone defects in an aged rat model. Collectively, these findings underscore the pivotal role of Y‐ECM in maintaining mitochondrial redox homeostasis and present a promising therapeutic strategy for the repair of aged bone defects. |
| format | Article |
| id | doaj-art-41b06c85c72e4d3db77c03e07dc4007c |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-41b06c85c72e4d3db77c03e07dc4007c2025-08-20T02:35:40ZengWileyAdvanced Science2198-38442025-03-011210n/an/a10.1002/advs.202409644Youthful Stem Cell Microenvironments: Rejuvenating Aged Bone Repair Through Mitochondrial Homeostasis RemodelingXinfeng Zhou0Xin Tian1Jianan Chen2Yantong Li3Nanning Lv4Hao Liu5Tao Liu6Huilin Yang7Xi Chen8Yong Xu9Fan He10Department of Orthopaedics The First Affiliated Hospital of Soochow University Orthopedic Institute MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopedic Institute MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopedic Institute MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopedic Institute MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopedic Institute MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopedic Institute MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopedic Institute MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopedic Institute MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaDepartment of Pathology The Third Affiliated Hospital of Soochow University Changzhou Jiangsu 213000 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopedic Institute MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopedic Institute MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaAbstract Extracellular matrix (ECM) derived from mesenchymal stem cells regulates antioxidant properties and bone metabolism by providing a favorable extracellular microenvironment. However, its functional role and molecular mechanism in mitochondrial function regulation and aged bone regeneration remain insufficiently elucidated. This proteomic analysis has revealed a greater abundance of proteins supporting mitochondrial function in the young ECM (Y‐ECM) secreted by young bone marrow‐derived mesenchymal stem cells (BMMSCs) compared to the aged ECM (A‐ECM). Further studies demonstrate that Y‐ECM significantly rejuvenates mitochondrial energy metabolism in adult BMMSCs (A‐BMMSCs) through the promotion of mitochondrial respiratory functions and amelioration of oxidative stress. A‐BMMSCs cultured on Y‐ECM exhibited enhanced multi‐lineage differentiation potentials in vitro and ectopic bone formation in vivo. Mechanistically, silencing of silent information regulator type 3 (SIRT3) gene abolished the protective impact of Y‐ECM on A‐BMMSCs. Notably, a novel composite biomaterial combining hyaluronic acid methacrylate hydrogel microspheres with Y‐ECM is developed, which yielded substantial improvements in the healing of bone defects in an aged rat model. Collectively, these findings underscore the pivotal role of Y‐ECM in maintaining mitochondrial redox homeostasis and present a promising therapeutic strategy for the repair of aged bone defects.https://doi.org/10.1002/advs.202409644aged bone defectsbone marrow‐derived mesenchymal stem cellsmitochondrial energy metabolismSIRT3youthful extracellular matrix |
| spellingShingle | Xinfeng Zhou Xin Tian Jianan Chen Yantong Li Nanning Lv Hao Liu Tao Liu Huilin Yang Xi Chen Yong Xu Fan He Youthful Stem Cell Microenvironments: Rejuvenating Aged Bone Repair Through Mitochondrial Homeostasis Remodeling Advanced Science aged bone defects bone marrow‐derived mesenchymal stem cells mitochondrial energy metabolism SIRT3 youthful extracellular matrix |
| title | Youthful Stem Cell Microenvironments: Rejuvenating Aged Bone Repair Through Mitochondrial Homeostasis Remodeling |
| title_full | Youthful Stem Cell Microenvironments: Rejuvenating Aged Bone Repair Through Mitochondrial Homeostasis Remodeling |
| title_fullStr | Youthful Stem Cell Microenvironments: Rejuvenating Aged Bone Repair Through Mitochondrial Homeostasis Remodeling |
| title_full_unstemmed | Youthful Stem Cell Microenvironments: Rejuvenating Aged Bone Repair Through Mitochondrial Homeostasis Remodeling |
| title_short | Youthful Stem Cell Microenvironments: Rejuvenating Aged Bone Repair Through Mitochondrial Homeostasis Remodeling |
| title_sort | youthful stem cell microenvironments rejuvenating aged bone repair through mitochondrial homeostasis remodeling |
| topic | aged bone defects bone marrow‐derived mesenchymal stem cells mitochondrial energy metabolism SIRT3 youthful extracellular matrix |
| url | https://doi.org/10.1002/advs.202409644 |
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