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      tsRNA-15797-modified BMSC-derived exosomes mediate LFNG to induce angiogenesis in osteonecrosis of the femoral head

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          Abstract

          Background

          Osteonecrosis of the femoral head (ONFH) is an ischemic disease characterized by the impairment of angiogenesis. We have previously elucidated the role of tsRNAs and BMSC exosomes in ONFH, but whether tsRNA-modified BMSC exosomes promote angiogenesis in ONFH remains unclear.

          Methods

          The expression of angiogenesis-related tsRNA in plasma exosomes from ONFH patients was examined by q-PCR. The function of tsRNA in HUVECs was identified by CCK-8 and angiogenesis assay. Exosomes purified from tsRNA-15797 overexpressed BMSCs were cocultured with HUVECs to examine their role in angiogenesis. The molecule mechanism of tsRNA-15797-modified exosomes was explored by RNA sequencing, dual-luciferase assay, and immunofluorescence.

          Results

          A tRNA-derived small RNA tsRNA-15797 was down-regulated in plasma exosomes of ONFH patients. We found the effects of BMSCs-derived exosomes on accelerating HUVECs angiogenesis and migration, which were further enhanced after overexpressing tsRNA-15797. Besides, overexpression of tsRNA-15797 would lead to down-regulation of LFNG correlated with angiogenesis. tsRNA-15797 could directly interact with LFNG. We demonstrated that LNFG overexpression weakened the pro angiogenic and migratory effects of tsRNA-15797-modified BMSCs-derived exosomes.

          Conclusion

          We successfully constructed tsRNA-15797-modified BMSC-derived exosomes and demonstrated that it induced the angiogenesis of HUVECs by targeting the down-regulation of LFNG. Thus, tsRNA-15797-loaded BMSCs-derived exosomes may be a potential target therapy drug for ONFH.

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          Most cited references39

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          The biology, function, and biomedical applications of exosomes

          Raghu Kalluri, Valerie LeBleu (2020)
          The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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            The m 6 A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation

            Tao Liu, Qinglv Wei, Jing Jin … (2020)
            Abstract N 6-Methyladenosine (m6A) is the most abundant RNA modification in mammal mRNAs and increasing evidence suggests the key roles of m6A in human tumorigenesis. However, whether m6A, especially its ‘reader’ YTHDF1, targets a gene involving in protein translation and thus affects overall protein production in cancer cells is largely unexplored. Here, using multi-omics analysis for ovarian cancer, we identified a novel mechanism involving EIF3C, a subunit of the protein translation initiation factor EIF3, as the direct target of the YTHDF1. YTHDF1 augments the translation of EIF3C in an m6A-dependent manner by binding to m6A-modified EIF3C mRNA and concomitantly promotes the overall translational output, thereby facilitating tumorigenesis and metastasis of ovarian cancer. YTHDF1 is frequently amplified in ovarian cancer and up-regulation of YTHDF1 is associated with the adverse prognosis of ovarian cancer patients. Furthermore, the protein but not the RNA abundance of EIF3C is increased in ovarian cancer and positively correlates with the protein expression of YTHDF1 in ovarian cancer patients, suggesting modification of EIF3C mRNA is more relevant to its role in cancer. Collectively, we identify the novel YTHDF1-EIF3C axis critical for ovarian cancer progression which can serve as a target to develop therapeutics for cancer treatment.
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              Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis

              Jieyuan Zhang, Junjie Guan, Xin Niu … (2015)
              Background Human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) have emerged as a promising alternative for stem cell transplantation therapy. Exosomes derived from mesenchymal stem cells (MSC-Exos) can play important roles in repairing injured tissues. However, to date, no reports have demonstrated the use of hiPSC-MSC-Exos in cutaneous wound healing, and little is known regarding their underlying mechanisms in tissue repair. Methods hiPSC-MSC-Exos were injected subcutaneously around wound sites in a rat model and the efficacy of hiPSC-MSC-Exos was assessed by measuring wound closure areas, by histological and immunofluorescence examinations. We also evaluated the in vitro effects of hiPSC-MSC-Exos on both the proliferation and migration of human dermal fibroblasts and human umbilical vein endothelial cells (HUVECs) by cell-counting and scratch assays, respectively. The effects of exosomes on fibroblast collagen and elastin secretion were studied in enzyme-linked immunosorbent assays and quantitative reverse-transcriptase–polymerase chain reaction (qRT-PCR). In vitro capillary network formation was determined in tube-formation assays. Results Transplanting hiPSC-MSC-Exos to wound sites resulted in accelerated re-epithelialization, reduced scar widths, and the promotion of collagen maturity. Moreover, hiPSC-MSC-Exos not only promoted the generation of newly formed vessels, but also accelerated their maturation in wound sites. We found that hiPSC-MSC-Exos stimulated the proliferation and migration of human dermal fibroblasts and HUVECs in a dose-dependent manner in vitro. Similarly, Type I, III collagen and elastin secretion and mRNA expression by fibroblasts and tube formation by HUVECs were also increased with increasing hiPSC-MSC-Exos concentrations. Conclusions Our findings suggest that hiPSC-MSC-Exos can facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. These data provide the first evidence for the potential of hiPSC-MSC-Exos in treating cutaneous wounds.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Turk J Biol
                Journal ID (iso-abbrev): Turk J Biol
                Title: Turkish Journal of Biology
                Publisher: Scientific and Technological Research Council of Turkey (TUBITAK)
                ISSN (Print): 1300-0152
                ISSN (Electronic): 1303-6092
                Publication date (Electronic, collection): 2023
                Publication date (Electronic, pub): 18 May 2023
                Volume: 47
                Issue: 3
                Pages: 186-198
                Affiliations
                [1 ]Department of Sports Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
                [2 ]Department of Orthopedic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
                Author notes
                [* ]Correspondence: chenpeng_1073@ 123456163.com
                Author information
                https://orcid.org/0000-0002-1277-0358
                Article
                Publisher ID: turkjbiol-47-3-186
                DOI: 10.55730/1300-0152.2654
                PMC ID: 10388130
                SO-VID: 3238cb91-b155-4502-b371-adac635239a6
                Copyright © © TÜBİTAK
                License:

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                Date received : 14 January 2023
                Date revision received : 21 June 2023
                Date accepted : 18 May 2023
                Funding
                Funded by: Joint Funds for the Innovation of Science and Technology, Fujian Province
                Award ID: 2020Y9116
                Funded by: Natural Science Foundation of Fujian Province
                Award ID: 2020J01964
                Funded by: Natural Science Foundation of Fujian Province
                Award ID: 2020J01948
                This research was supported by Joint Funds for the Innovation of Science and Technology, Fujian Province (No.2020Y9116), the Natural Science Foundation of Fujian Province (No. 2020J01964), and the Natural Science Foundation of Fujian Province (No. 2020J01948).
                Categories
                Subject: Research Article

                Keywords: osteonecrosis of the femoral head,tsrna-15797,exosomes,angiogenesis
                Data availability:
                Keywords: osteonecrosis of the femoral head, tsrna-15797, exosomes, angiogenesis

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