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Cited by 310Extracellular vesicles in diseaseOsteoarthritis Treatment and MechanismsMesenchymal stem cell research

miR‐23a‐3p‐abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration

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Hu, Hongxing, Dong, Lanlan, Bu, Ziheng, Shen, Yifan, Luo, Jian, Zhang, Hang, Zhao, Shichang, Lv, Fang +1 more·2020·Journal of Extracellular Vesicles
DOI 10.1080/20013078.2020.1778883PMC PMC7480606
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Abstract

Articular cartilage has limited self‐regenerative capacity and the therapeutic methods for cartilage defects are still dissatisfactory in clinic. Recent studies showed that exosomes derived from mesenchymal stem cells promoted chondrogenesis by delivering bioactive substances to the recipient cells, indicating exosomes might be a novel method for repairing cartilage defect. Herein, we investigated the role and mechanism of human umbilical cord mesenchymal stem cells derived small extracellular vesicles (hUC‐MSCs‐sEVs) on cartilage regeneration. In vitro results showed that hUC‐MSCs‐sEVs promoted the migration, proliferation and differentiation of chondrocytes and human bone marrow mesenchymal stem cells (hBMSCs). MiRNA microarray showed that miR‐23a‐3p was the most highly expressed among the various miRNAs contained in hUC‐MSCs‐sEVs. Our data revealed that hUC‐MSCs‐sEVs promoted cartilage regeneration by transferring miR‐23a‐3p to suppress the level of PTEN and elevate expression of AKT. Moreover, we fabricated Gelatin methacrylate (Gelma)/nanoclay hydrogel (Gel‐nano) for sustained release of sEVs, which was biocompatible and exhibited excellent mechanical property. In vivo results showed that hUC‐MSCs‐sEVs containing Gelma/nanoclay hydrogel (Gel‐nano‐sEVs) effectively promoted cartilage regeneration. These results indicated that Gel‐nano‐sEVs have a promising capacity to stimulate chondrogenesis and heal cartilage defects, and also provided valuable data for understanding the role and mechanism of hUC‐MSCs‐sEVs in cartilage regeneration.

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  • During human cartilage regeneration, expression level of miR-23a-3p in small extracellular vesicles derived from umbilical cord mesenchymal stem cells was significantly ramped up, inhibiting PTEN.

    “during human cartilage regeneration, the expression level of miR-23a-3p in small extracellular vesicles derived from umbilical cord mesenchymal stem cells was significantly ramped up, inhibiting the expression level of PTEN.”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [112]

    The Results section reports that vesicles from human umbilical cord mesenchymal stem cells delivered miR-23a-3p into chondrocytes and human bone marrow mesenchymal stem cells, where miR-23a-3p increased and PTEN decreased. It does not report that miR-23a-3p expression increased within the vesicles during human cartilage regeneration; its microarray finding is that miR-23a-3p was the most highly expressed miRNA in those vesicles. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Human hemoglobin combined with vesicles-derived miR-23a-3p overexpression through gel scaffold can repair and reconstruct bone through the PTEN/AKT signal pathway, and promote osteogenesis and angiogenesis.

    “Human hemoglobin combined with vesicles-derived miR-23a-3p overexpression through gel scaffold can repair and reconstruct bone through PTEN/AKT signal pathway, and promote osteogenesis and angiogenesis [[111], [112], [113]].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [112]

    The Results section reports that vesicle-delivered miR-23a-3p targets PTEN and activates AKT signalling; the Discussion reports cartilage regeneration using a Gelma/nanoclay hydrogel. The paper does not report a human-hemoglobin combination, bone reconstruction, osteogenesis, or angiogenesis. Page numbers were not provided in our copy. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Within the first 24 h of osteoclast formation, the miR-23 family displayed differential downregulation between undifferentiated cells and macrophages stimulated by RANKL.

    “Within the first 24 h of osteoclast formation, the miR-23 family displayed differential downregulation between undifferentiated cells and macrophages stimulated by receptor activator of nuclear factor-B ligand (RANKL).”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [112]

    The Results discuss miR-23a-3p in chondrocytes and hBMSCs, including a 24-hour chondrocyte experiment, but do not address osteoclast formation. Searches for RANKL-stimulated macrophages and first-24-hour miR-23-family downregulation found no passage supporting the claim in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Authors
Hu, H., Dong, L., Bu, Z., Shen, Y., Luo, J., Zhang, H., Zhao, S., Lv, F., & Liu, Z.
Affiliations
  • Wenzhou Medical University (CN)
  • Shanghai Jiao Tong University (CN)
  • Second Military Medical University (CN)
  • East China Normal University (CN)
  • Southern Medical University (CN)
Corresponding author
  • Zhao, Shichang
  • Lv, Fang
  • Liu, Zhongtang
ORCID
Venue
Journal of Extracellular Vesicles
Publisher
Wiley
Published
2020-06-16
Volume
9
Issue
1
Pages
1778883-1778883
ISSN
2001-3078 (ISSN-L)
DOI
10.1080/20013078.2020.1778883
PMC
PMC7480606
OpenAlex
W3034592342
Cited by
310
References
55
Citations by year
2026: 28 · 2025: 58 · 2024: 84 · 2023: 50 · 2022: 57 · 2021: 30 · 2020: 3
FWCI
11.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Extracellular Vesicles (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Key Research and Development Program of China (2018YFC1105102)
  • National Natural Science Foundation of China (51673212, 51972212, 81802202)
  • by National Key Research and Development Program of China
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
cartilage regeneration, small extracellular vesicles, miR-23a-3p, human umbilical cord mesenchymal stem cells, sustained drug release, chondrogenesis, PTEN, Akt, exosomes, cartilage defects, bone marrow mesenchymal stem cells

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