Exosomes derived from miR‐375‐overexpressing human adipose mesenchymal stem cells promote bone regeneration
Open accessAbstract
OBJECTIVES: The present study aimed to investigate whether exosomes derived from miR-375-overexpressing human adipose mesenchymal stem cells (hASCs) could enhance bone regeneration. MATERIALS AND METHODS: Exosomes enriched with miR-375 (Exo [miR-375]) were generated from hASCs stably overexpressing miR-375 after lentiviral transfection and identified with transmission electron microscopy, nanosight and western blotting. The construction efficiency of Exo (miR-375) was evaluated with qRT-PCR and incubated with human bone marrow mesenchymal stem cells (hBMSCs) to optimize the effective dosage. Then, the osteogenic capability of Exo (miR-375) was investigated with ALP and ARS assays. Furthermore, dual-luciferase reporter assay and western blotting were conducted to reveal the underlying mechanism of miR-375 in osteogenic regulation. Finally, Exo (miR-375) were embedded with hydrogel and applied to a rat model of calvarial defect, and μ-CT analysis and histological examination were conducted to evaluate the therapeutic effects of Exo (miR-375) in bone regeneration. RESULTS: miR-375 could be enriched in exosomes by overexpressing in the parent cells. Administration of Exo (miR-375) at 50 μg/mL improved the osteogenic differentiation of hBMSCs. With miR-375 absorbed by hBMSCs, insulin-like growth factor binding protein 3 (IGFBP3) was inhibited by binding to its 3'UTR, and recombinant IGFBP3 protein reduced the osteogenic effects triggered by Exo (miR-375). After incorporated with hydrogel, Exo (miR-375) displayed a slow and controlled release, and further in vivo analysis demonstrated that Exo (miR-375) enhanced the bone regenerative capacity in a rat model of calvarial defect. CONCLUSIONS: Taken together, our study demonstrated that exosomes derived from miR-375-overexpressing hASCs promoted bone regeneration.
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Exosomes promoted hBMSC osteogenic differentiation through exosomal miR-375.
“exosomes promoted hBMSC osteogenic differentiation through exosomal miR-375 [66].”
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Self-citation
- Authors
- Chen, S., Tang, Y., Liu, Y., Zhang, P., Lv, L., Zhang, X., Jia, L., & Zhou, Y.
- Affiliations
- Peking University (CN)
- Peking University School and Hospital of Stomatology (CN)
- Corresponding author
- Jia, Lingfei
- Zhou, Yongsheng
- Venue
- Cell Proliferation
- Publisher
- Wiley
- Published
- 2019-08-05
- Volume
- 52
- Issue
- 5
- Pages
- e12669-e12669
- ISSN
- 0960-7722 (ISSN-L)
- 1365-2184
- PMC
- PMC6797519
- OpenAlex
- W2965584378
- Cited by
- 344
- References
- 50
- Citations by year
- 2026: 18 · 2025: 44 · 2024: 59 · 2023: 55 · 2022: 71 · 2021: 60 · 2020: 36 · 2019: 1
- FWCI
- 13.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Proliferation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81600834, 81772876)
- Natural Science Foundation of Beijing Municipality (L182006)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- exosomes, miR-375, adipose-derived stem cells, bone regeneration, osteogenic differentiation, bone marrow mesenchymal stem cells, IGFBP-3, microRNA delivery, hydrogels, calvarial defect, 3' UTR binding
- MeSH terms
- Adipose Tissue, Animals, Bone Regeneration, Cell Differentiation, Cells, Cultured, Humans, Male, Osteogenesis, Recombinant Proteins, Skull, Skull Fractures, Rats, Sprague-Dawley, Insulin-Like Growth Factor Binding Protein 3, Hydrogels, 3' Untranslated Regions, MicroRNAs, Cell Proliferation, Rats, Exosomes, Mesenchymal Stem Cells
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