摘要
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.
基金
supported by grants from the National Natural Science Foundation of China(No.82170929 and 81970908 to Y.L.)
the Beijing Natural Science Foundation(No.7222224 to X.Z.)。
