Altered MicroRNA Expression Profile in Exosomes during Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells
Open accessAbstract
The physiological role of microRNAs (miRNAs) in osteoblast differentiation remains elusive. Exosomal miRNAs isolated from human bone marrow-derived mesenchymal stem cells (BMSCs) culture were profiled using miRNA arrays containing probes for 894 human matured miRNAs. Seventy-nine miRNAs (∼8.84%) could be detected in exosomes isolated from BMSC culture supernatants when normalized to endogenous control genes RNU44. Among them, nine exosomal miRNAs were up regulated and 4 miRNAs were under regulated significantly (Relative fold>2, p<0.05) when compared with the values at 0 day with maximum changes at 1 to 7 days. Five miRNAs (miR-199b, miR-218, miR-148a, miR-135b, and miR-221) were further validated and differentially expressed in the individual exosomal samples from hBMSCs cultured at different time points. Bioinformatic analysis by DIANA-mirPath demonstrated that RNA degradation, mRNA surveillance pathway, Wnt signaling pathway, RNA transport were the most prominent pathways enriched in quantiles with differential exosomal miRNA patterns related to osteogenic differentiation. These data demonstrated exosomal miRNA is a regulator of osteoblast differentiation.
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miRNAs carried within EVs originating from MSCs have been identified as pivotal agents in orchestrating angiogenesis and cellular differentiation towards osteoblasts.
“Notably, microRNAs (miRNAs) carried within EVs originating from MSCs have been identified as pivotal agents in orchestrating angiogenesis and cellular differentiation towards osteoblasts, two key processes for bone formation.”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [50]
The Discussion reports miRNAs in exosomes from human BMSCs and links several of those miRNAs to osteogenic differentiation, but says their functions as exosome-associated miRNAs require future investigation. Its angiogenesis example concerns exosomes from hypoxic tumor cells, not miRNAs in MSC-derived exosomes. The source therefore does not support the claim that MSC-derived exosomal miRNAs orchestrate angiogenesis. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThese miRNAs are regulators of various signaling pathways, including RNA degradation, mRNA surveillance, and the Wnt signaling pathway, contributing to the facilitation of osteogenesis.
“These miRNAs are regulators of various signaling pathways, including RNA degradation, mRNA surveillance, and the Wnt signaling pathway, contributing to the facilitation of osteogenesis [49,50].”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [50]
The Comparative pathway analyses and Discussion link differentially expressed exosomal miRNAs to RNA degradation, mRNA surveillance, and Wnt signaling, but describe those links as pathway enrichment and a possible regulatory function. They do not establish that the miRNAs collectively facilitate osteogenesis; the Results instead identify miR-885-5p as a negative regulator of osteogenic differentiation. Page numbers were not supplied in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredmiRNA cargos in EVs derived from BM-MSCs undergoing osteogenic differentiation include let-7a, miR-199b, miR-218, miR-148a, miR-135b, miR-203, miR-219, miR-299-5p, and miR-302b.
“Recent studies offer insight into the significance of miRNAs cargos in EVs derived from BM-MSCs undergoing osteogenic differentiation, such as let-7a, miR-199b, miR-218, miR-148a, miR-135b, miR-203, miR-219, miR-299-5p, and miR-302b [49,50].”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [50]
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Self-citation
- Authors
- Xu, J.-F., Yang, G.-H., Pan, X.-H., Zhang, S.-J., Zhao, C., Qiu, B.-S., Gu, H.-F., Hong, J.-F., Cao, L., Chen, Y., Xia, B., Bi, Q., & Wang, Y.-P.
- Affiliations
- Zhejiang Provincial People's Hospital (CN)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-12-11
- Volume
- 9
- Issue
- 12
- Pages
- e114627
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4263734
- OpenAlex
- W2005323891
- Cited by
- 235
- References
- 60
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 20 · 2023: 15 · 2022: 18 · 2021: 32 · 2020: 26 · 2019: 26 · 2018: 27 · 2017: 28 · 2016: 19 · 2015: 6
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (Grant No. 81200113, 81200113)
- Medical Scientific Research Foundation of Zhejiang Province, China (2013KYB031, Grant No. 2013KYB031)
- Fundamental Research Funds for the Central Universities (Grant No. 2014FZA7014)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- microRNA, exosomes, osteogenic differentiation, bone marrow-derived mesenchymal stem cells, miR-199b, miR-218, miR-148a, miR-135b, miR-221, Wnt signaling, mRNA surveillance, RNA transport, extracellular vesicles
- MeSH terms
- Adult, Cell Differentiation, Female, Humans, Male, Osteogenesis, RNA, Messenger, Reproducibility of Results, MicroRNAs, Exosomes, Bone Morphogenetic Protein 2, Transcriptome, Mesenchymal Stem Cells
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