Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance
BackgroundDiabetes mellitus is a chronic metabolic disease with systemic complications. Patient with diabetes have increased risks of bone fracture. Previous studies report that diabetes could affect bone metabolism, however, the underlying mechanism is still unclear.MethodsWe isolated exosomes secr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1149168/full |
| _version_ | 1797847202723266560 |
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| author | Fei Han Fei Han Chao Wang Chao Wang Peng Cheng Ting Liu Wei-Shan Wang Wei-Shan Wang |
| author_facet | Fei Han Fei Han Chao Wang Chao Wang Peng Cheng Ting Liu Wei-Shan Wang Wei-Shan Wang |
| author_sort | Fei Han |
| collection | DOAJ |
| description | BackgroundDiabetes mellitus is a chronic metabolic disease with systemic complications. Patient with diabetes have increased risks of bone fracture. Previous studies report that diabetes could affect bone metabolism, however, the underlying mechanism is still unclear.MethodsWe isolated exosomes secreted by bone marrow mesenchymal stem cells of normal and diabetic mice and test their effects on osteogenesis and adipogenesis. Then we screened the differential microRNAs by high-throughput sequencing and explored the function of key microRNA in vitro and in vivo.ResultsWe find that lower bone mass and higher marrow fat accumulation, also called bone-fat imbalance, exists in diabetic mouse model. Exosomes secreted by normal bone marrow mesenchymal stem cells (BMSCs-Exos) enhanced osteogenesis and suppressed adipogenesis, while these effects were diminished in diabetic BMSCs-Exos. miR-221, as one of the highly expressed miRNAs within diabetic BMSCs-Exos, showed abilities of suppressing osteogenesis and promoting adipogenesis both in vitro and in vivo. Elevation of miR-221 level in normal BMSCs-Exos impairs the ability of regulating osteogenesis and adipogenesis. Intriguingly, using the aptamer delivery system, delivery normal BMSCs-Exos specifically to BMSCs increased bone mass, reduced marrow fat accumulation, and promoted bone regeneration in diabetic mice.ConclusionWe demonstrate that BMSCs derived exosomal miR-221 is a key regulator of diabetic osteoporosis, which may represent a potential therapeutic target for diabetes-related skeletal disorders. |
| first_indexed | 2024-04-09T18:08:36Z |
| format | Article |
| id | doaj.art-0888183a7bd348528d1f766f262f70e9 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-09T18:08:36Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-0888183a7bd348528d1f766f262f70e92023-04-14T04:43:38ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-04-011410.3389/fendo.2023.11491681149168Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalanceFei Han0Fei Han1Chao Wang2Chao Wang3Peng Cheng4Ting Liu5Wei-Shan Wang6Wei-Shan Wang7Medical College, Shihezi University, Shihezi, Xinjiang, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang, ChinaMedical College, Shihezi University, Shihezi, Xinjiang, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang, ChinaDivision of Geriatric Endocrinology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Endocrinology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, ChinaMedical College, Shihezi University, Shihezi, Xinjiang, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang, ChinaBackgroundDiabetes mellitus is a chronic metabolic disease with systemic complications. Patient with diabetes have increased risks of bone fracture. Previous studies report that diabetes could affect bone metabolism, however, the underlying mechanism is still unclear.MethodsWe isolated exosomes secreted by bone marrow mesenchymal stem cells of normal and diabetic mice and test their effects on osteogenesis and adipogenesis. Then we screened the differential microRNAs by high-throughput sequencing and explored the function of key microRNA in vitro and in vivo.ResultsWe find that lower bone mass and higher marrow fat accumulation, also called bone-fat imbalance, exists in diabetic mouse model. Exosomes secreted by normal bone marrow mesenchymal stem cells (BMSCs-Exos) enhanced osteogenesis and suppressed adipogenesis, while these effects were diminished in diabetic BMSCs-Exos. miR-221, as one of the highly expressed miRNAs within diabetic BMSCs-Exos, showed abilities of suppressing osteogenesis and promoting adipogenesis both in vitro and in vivo. Elevation of miR-221 level in normal BMSCs-Exos impairs the ability of regulating osteogenesis and adipogenesis. Intriguingly, using the aptamer delivery system, delivery normal BMSCs-Exos specifically to BMSCs increased bone mass, reduced marrow fat accumulation, and promoted bone regeneration in diabetic mice.ConclusionWe demonstrate that BMSCs derived exosomal miR-221 is a key regulator of diabetic osteoporosis, which may represent a potential therapeutic target for diabetes-related skeletal disorders.https://www.frontiersin.org/articles/10.3389/fendo.2023.1149168/fulldiabetesosteoporosisbone-fat imbalanceexosomesmiR-221 |
| spellingShingle | Fei Han Fei Han Chao Wang Chao Wang Peng Cheng Ting Liu Wei-Shan Wang Wei-Shan Wang Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance Frontiers in Endocrinology diabetes osteoporosis bone-fat imbalance exosomes miR-221 |
| title | Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance |
| title_full | Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance |
| title_fullStr | Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance |
| title_full_unstemmed | Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance |
| title_short | Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance |
| title_sort | bone marrow mesenchymal stem cells derived exosomal mirnas can modulate diabetic bone fat imbalance |
| topic | diabetes osteoporosis bone-fat imbalance exosomes miR-221 |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1149168/full |
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