Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake

• Published in: International journal of oral science 2024-04, Vol.16 (1), p.31-31, Article 31
• Main Authors: Cheng, Yawen, Zhu, Yuan, Liu, Yaoshan, Liu, Xuenan, Ding, Yanan, Li, Deli, Zhang, Xiao, Liu, Yunsong
• Format: Article
• Language: English
• Subjects: 631/532/1360; 631/532/2074; Adipogenesis; AKT protein; Apoptosis; Bone growth; Bone Regeneration; Dentistry; Exosomes; Exosomes - genetics; Exosomes - metabolism; Extracellular Vesicles - metabolism; Medicine; Mesenchymal stem cells; MicroRNAs; MicroRNAs - genetics; miRNA; Oral and Maxillofacial Surgery; Orthopedics; Osteogenesis; Regeneration; Surgical Orthopedics; Vesicles
• ISSN: 2049-3169; 1674-2818; 2049-3169
• DOI: 10.1038/s41368-024-00293-0

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.