Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake
Abstract Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoin...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-04-01
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| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-024-00293-0 |
| _version_ | 1797199626886971392 |
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| author | Yawen Cheng Yuan Zhu Yaoshan Liu Xuenan Liu Yanan Ding Deli Li Xiao Zhang Yunsong Liu |
| author_facet | Yawen Cheng Yuan Zhu Yaoshan Liu Xuenan Liu Yanan Ding Deli Li Xiao Zhang Yunsong Liu |
| author_sort | Yawen Cheng |
| collection | DOAJ |
| description | Abstract Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration. |
| first_indexed | 2024-04-24T07:18:45Z |
| format | Article |
| id | doaj.art-a97ffbd121e24120aea0648cd60d14e2 |
| institution | Directory Open Access Journal |
| issn | 2049-3169 |
| language | English |
| last_indexed | 2024-04-24T07:18:45Z |
| publishDate | 2024-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj.art-a97ffbd121e24120aea0648cd60d14e22024-04-21T11:10:50ZengNature Publishing GroupInternational Journal of Oral Science2049-31692024-04-0116111410.1038/s41368-024-00293-0Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brakeYawen Cheng0Yuan Zhu1Yaoshan Liu2Xuenan Liu3Yanan Ding4Deli Li5Xiao Zhang6Yunsong Liu7Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital StomatologyDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital StomatologyDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital StomatologyDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital StomatologyDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital StomatologySecond Clinical Division, Peking University School and Hospital of StomatologyDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital StomatologyDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital StomatologyAbstract Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.https://doi.org/10.1038/s41368-024-00293-0 |
| spellingShingle | Yawen Cheng Yuan Zhu Yaoshan Liu Xuenan Liu Yanan Ding Deli Li Xiao Zhang Yunsong Liu Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake International Journal of Oral Science |
| title | Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake |
| title_full | Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake |
| title_fullStr | Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake |
| title_full_unstemmed | Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake |
| title_short | Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake |
| title_sort | tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake |
| url | https://doi.org/10.1038/s41368-024-00293-0 |
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