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      Is Open Access

      Exosomes May Be the Potential New Direction of Research in Osteoarthritis Management

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          Abstract

          Osteoarthritis (OA) is a joint degenerative disease, which is prominent in the middle-aged and elderly population, often leading to repeated pain in the joints of patients and seriously affecting the life quality of patients. At present, the treatment of OA mainly depends on the surgery and drug treatment. Nevertheless, these treatments still face many problems, such as surgical safety, complications, and drug side effects. Exosomes can be secreted and released by multiple cell types and have lipid bilayer membranes and contain abundant biological molecules, including proteins, lipids, and nucleic acids. Moreover, exosomes play a critical role in local and distal intercellular and intracellular communication. In recent years, several studies have found that exosomes can regulate the progression of OA and have a potential efficacy for OA treatment. Thus, in this article, we summarize and review the relevant research of exosomes in OA and emphasize the importance of exosomes in the development of OA.

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          Most cited references44

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          Extracellular vesicle isolation and characterization: toward clinical application.

          Two broad categories of extracellular vesicles (EVs), exosomes and shed microvesicles (sMVs), which differ in size distribution as well as protein and RNA profiles, have been described. EVs are known to play key roles in cell-cell communication, acting proximally as well as systemically. This Review discusses the nature of EV subtypes, strategies for isolating EVs from both cell-culture media and body fluids, and procedures for quantifying EVs. We also discuss proteins selectively enriched in exosomes and sMVs that have the potential for use as markers to discriminate between EV subtypes, as well as various applications of EVs in clinical diagnosis.
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            Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model

            OBJECTIVES: Osteoarthritis (OA) is the most common joint disease throughout the world. Exosomes derived from miR-140-5p-overexpressing synovial mesenchymal stem cells (SMSC-140s) may be effective in treating OA. We hypothesized that exosomes derived from SMSC-140 (SMSC-140-Exos) would enhance the proliferation and migration abilities of articular chondrocytes (ACs) without harming extracellular matrix (ECM) secretion. METHODS: SMSCs were transfected with or without miR-140-5p. Exosomes derived from SMSCs or SMSC-140s (SMSC-Exos or SMSC-140-Exos) were isolated and identified. Proliferation, migration and ECM secretion were measured in vitro and compared between groups. The mechanism involving alternative Wnt signalling and activation of Yes-associated protein (YAP) was investigated using lentivirus, oligonucleotides or chemical drugs. The preventative effect of exosomes in vivo was measured using Safranin-O and Fast green staining and immunohistochemical staining. RESULTS: Wnt5a and Wnt5b carried by exosomes activated YAP via the alternative Wnt signalling pathway and enhanced proliferation and migration of chondrocytes with the side-effect of significantly decreasing ECM secretion. Highly-expressed miR-140-5p blocked this side-effect via RalA. SMSC-140-Exos enhanced the proliferation and migration of ACs without damaging ECM secretion in vitro, while in vivo, SMSC-140-Exos successfully prevented OA in a rat model. CONCLUSIONS: These findings highlight the promising potential of SMSC-140-Exos in preventing OA. We first found a potential source of exosomes and studied their merits and shortcomings. Based on our understanding of the molecular mechanism, we overcame the shortcomings by modifying the exosomes. Such exosomes derived from modified cells hold potential as future therapeutic strategies.
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              miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis

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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2019
                3 November 2019
                : 2019
                : 7695768
                Affiliations
                1Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, China
                2Department of Orthopedics, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, China
                3Nanchang Key Laboratory of Orthopaedics, The Third Affiliated Hospital of Nanchang University, Nanchang, China
                4Medical Department of Graduate School, Nanchang University, Nanchang, Jiangxi 330006, China
                Author notes

                Academic Editor: Despina Deligianni

                Author information
                https://orcid.org/0000-0002-6469-6946
                https://orcid.org/0000-0002-4966-5770
                https://orcid.org/0000-0002-5212-6487
                https://orcid.org/0000-0002-6137-4888
                https://orcid.org/0000-0002-8519-999X
                https://orcid.org/0000-0001-7424-0339
                https://orcid.org/0000-0002-0000-3063
                Article
                10.1155/2019/7695768
                6875272
                31781642
                2d8b651f-be5c-43de-bc6c-7dbb366508dc
                Copyright © 2019 Cheng Ju et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 August 2019
                : 5 October 2019
                : 14 October 2019
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81560452
                Award ID: 81672866
                Funded by: Natural Science Foundation of Jiangxi Province
                Award ID: 20161BAB205192
                Award ID: 20171ACB21073
                Funded by: Youth Science Foundation of Jiangxi Province
                Award ID: 20122BAB215028
                Categories
                Review Article

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