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      Role of MicroRNA, LncRNA, and Exosomes in the Progression of Osteoarthritis: A Review of Recent Literature

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          Abstract

          Osteoarthritis (OA) is a common clinical degenerative disease characterized by the destruction of articular cartilage, which has an increasing impact on people's lives and social economy. The pathogenesis of OA is complex and unclear, and there is no effective way to block its progress. The study of the pathogenesis of OA is the prerequisite for the early diagnosis and effective treatment of OA. To define the pathogenesis of OA, this review considers the pathological mechanism of OA that involves microRNA, lncRNA, and exosomes. More and more evidence shows that microRNA, lncRNA, and exosomes are closely related to OA. MicroRNA inhibits the target gene by binding to the 3′‐ untranslated region of the targets. LncRNA usually competes with microRNA to regulate the expression level of downstream genes, while exosomes, as a carrier of intercellular information transfer, transmit the biological information of mother cells to target cells, and the effect of exosomes secreted by different cells on OA are different. In this review, we emphasized that different microRNA, lncRNA, and exosomes have different regulatory effects on chondrocyte proliferation and apoptosis, extracellular matrix degradation and inflammation. Besides, we classified and analyzed these molecules according to their effects on the progress of OA. Based on the analysis of the reported literature, this review reveals some pathogenesis of OA, and emphasizes that microRNA, lncRNA, and exosomes have great potential to assist early diagnosis and effective treatment of OA.

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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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              Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A

              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. Electronic supplementary material The online version of this article (10.1186/s13287-018-1004-0) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                13973657615@139.com
                yhywgb@126.com
                Journal
                Orthop Surg
                Orthop Surg
                10.1111/(ISSN)1757-7861
                OS
                Orthopaedic Surgery
                John Wiley & Sons Australia, Ltd (Melbourne )
                1757-7853
                1757-7861
                20 May 2020
                June 2020
                : 12
                : 3 ( doiID: 10.1111/os.v12.3 )
                : 708-716
                Affiliations
                [ 1 ] Affiliated Changde Hospital Hunan University of Traditional Chinese Medicine Changde China
                [ 2 ] Department of Orthopaedics Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine Changsha China
                Author notes
                [*] [* ] Address for correspondence Xian‐fang Shao, MD, Affiliated Changde Hospital, Hunan University of Traditional Chinese Medicine, No.588 of Binhu Road, Changde, China 415000; Tel:+86‐0736‐7893888; Email: 13973657615@ 123456139.com , Guan‐bao Wu, MD, Department of Orthopaedics, Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, No.58 of Lushan Road, Yuelu District, Changsha, China 410006; Tel:+86‐0731‐88854064; Email: yhywgb@ 123456126.com
                [*]

                These authors contributed equally to this study.

                Author information
                https://orcid.org/0000-0002-0039-8747
                Article
                OS12690
                10.1111/os.12690
                7307224
                32436304
                e967a1b3-09be-4a13-aaa7-4fbaec92c885
                © 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 February 2020
                : 27 March 2020
                : 27 March 2020
                Page count
                Figures: 3, Tables: 2, Pages: 9, Words: 7721
                Funding
                Funded by: Changde Science and Technology Bureau
                Award ID: 2012SK06
                Funded by: Hunan Administration of Traditional Chinese Medicine
                Award ID: 201902
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 81874476
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                June 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:22.06.2020

                exosomes,lncrna,microrna,osteoarthritis
                exosomes, lncrna, microrna, osteoarthritis

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