The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A
Open accessAbstract
BACKGROUND: WNT5A is known to be involved in the pathogenesis of osteoarthritis. This study investigated the molecular mechanism of exosomal miR-92a-3p and WNT5A in chondrogenesis and cartilage degeneration. METHODS: Exosomal miR-92a-3p expression was assessed in vitro in a human mesenchymal stem cell (MSC) model of chondrogenesis and in normal and OA primary human chondrocytes (PHCs). MSCs and PHCs were treated with exosomes derived from MSC-miR-92a-3p (MSC-miR-92a-3p-Exos) or its antisense inhibitor (MSC-anti-miR-92a-3p-Exos), respectively. Small interfering RNAs (siRNAs) and luciferase reporter assay were used to reveal the molecular role of exosomal miR-92a-3p and WNT5A in chondrogenesis. The protective effect of exosomes in vivo was measured using Safranin-O and Fast Green staining and immunohistochemical staining. RESULTS: Exosomal miR-92a-3p expression was elevated in the MSC chondrogenic exosome, while it was significantly reduced in the OA chondrocyte-secreted exosome compared with normal cartilage. Treatment with MSC-miR-92a-3p-Exos promoted cartilage proliferation and matrix genes expression in MSCs and PHCs, respectively. In contrast, treatment with MSC-anti-miR-92a-3p-Exos repressed chondrogenic differentiation and reduced cartilage matrix synthesis by enhancing the expression of WNT5A. Luciferase reporter assay demonstrated that miR-92a-3p suppressed the activity of a reporter construct containing the 3'-UTR and inhibited WNT5A expression in both MSCs and PHCs. MSC-miR-92a-3p-Exos inhibit cartilage degradation in the OA mice model. CONCLUSIONS: Our results suggest that exosomal miR-92a-3p regulates cartilage development and homeostasis by directly targeting WNT5A. This indicates that exosomal miR-92a-3p may act as a Wnt inhibitor and exhibits potential as a disease-modifying osteoarthritis drug.
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Cites
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The biology , function , and biomedical applications of exosomes
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Clinical applications of stem cell-derived exosomes
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Mesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis?
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Metadata
- Authors
- Mao, G., Zhang, Z., Hu, S., Zhang, Z., Chang, Z., Huang, Z., Liao, W., & Kang, Y.
- Venue
- Stem Cell Research & Therapy
- Published
- 2018-09-26
- Volume
- 9
- Issue
- 1
- Pages
- 247-247
- ISSN
- 1757-6512 (ISSN-L)
- OpenAlex
- W2893768232
- Cited by
- 462
- References
- 46
- FWCI
- 30.09
- Type
- journal article
- Language
- en
- Open access
- gold
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- Mao, G., Zhang, Z., Hu, S., Zhang, Z., Chang, Z., Huang, Z., Liao, W., & Kang, Y. (2018). Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-018-1004-0
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