{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:52:29Z","timestamp":1793332349360,"version":"4.5.0"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) may play a vital role in a variety of biological processes, including cartilage regeneration. However, few studies reported their potential in the development of osteoarthritis (OA) previously. In this study, we explored the biological roles and underlying mechanism of MSCs-EVs in OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Co-culture experiments revealed that MSCs-EVs could promote the expression of collagen type II alpha 1 chain (COL2A1), SRY-box transcription factor 9 (SOX9) and Aggrecan while negatively regulate the expression of chondrocyte hypertrophy markers matrix metallopeptidase 13 (MMP-13) and RUNX family transcription factor 2 (Runx2) in mouse chondrocytes in the OA model. Besides, the results of cell experiments indicated that MSCs-EVs could notably weaken the suppression of chondrocyte proliferation, migration and the promotion of chondrocyte apoptosis via interleukin1\u03b2 (IL-1\u03b2) induction. In addition, MSCs-circHIPK3-EVs (EVs derived from MSCs overexpressing circHIPK3) considerably improved IL-1\u03b2-induced chondrocyte injury. Mechanistically, we elucidated that circHIPK3 could directly bind to miR-124-3p and subsequently elevate the expression of the target gene MYH9.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings in our study demonstrated that EVs-circHIPK3 participated in MSCs-EVs-mediated chondrocyte proliferation and migration induction and in chondrocyte apoptosis inhibition via the miR-124-3p\/MYH9 axis. This offers a promising novel cell-free therapy for treating OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphic abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s12951-021-00940-2","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T04:02:55Z","timestamp":1625025775000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3\/miR-124-3p\/MYH9 axis"],"prefix":"10.1186","volume":"19","author":[{"given":"Shenglong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"940_CR1","doi-asserted-by":"crossref","first-page":"1759720X2098121","DOI":"10.1177\/1759720X20981219","volume":"12","author":"CG de Campos","year":"2020","unstructured":"de Campos CG, Mundi R, Whittington C, Toutounji MJ, Ngai W, Sheehan B. Osteoarthritis, mobility-related comorbidities and mortality: an overview of meta-analyses. Ther Adv Musculoskelet Dis. 2020;12:1759720X20981219.","journal-title":"Ther Adv Musculoskelet Dis."},{"key":"940_CR2","doi-asserted-by":"publisher","first-page":"560117","DOI":"10.3389\/fcell.2020.560117","volume":"8","author":"H Zhang","year":"2020","unstructured":"Zhang H, Ji L, Yang Y, Zhang X, Gang Y, Bai L. The role of HDACs and HDACi in cartilage and osteoarthritis. Front Cell Dev Biol. 2020;8:560117.","journal-title":"Front Cell Dev Biol"},{"key":"940_CR3","doi-asserted-by":"publisher","first-page":"608388","DOI":"10.3389\/fcell.2020.608388","volume":"8","author":"R Duan","year":"2020","unstructured":"Duan R, Xie H, Liu ZZ. The role of autophagy in osteoarthritis. Front Cell Dev Biol. 2020;8:608388.","journal-title":"Front Cell Dev Biol"},{"key":"940_CR4","doi-asserted-by":"publisher","first-page":"577015","DOI":"10.3389\/fimmu.2020.577015","volume":"11","author":"M Hasegawa","year":"2020","unstructured":"Hasegawa M, Yoshida T, Sudo A. Tenascin-C in osteoarthritis and rheumatoid arthritis. Front Immunol. 2020;11:577015.","journal-title":"Front Immunol"},{"key":"940_CR5","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.jconrel.2020.11.007","volume":"328","author":"S Xiao","year":"2020","unstructured":"Xiao S, Chen L. The emerging landscape of nanotheranostic-based diagnosis and therapy for osteoarthritis. J Control Release. 2020;328:817\u201333.","journal-title":"J Control Release"},{"key":"940_CR6","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.14336\/AD.2019.1116","volume":"11","author":"N Zeng","year":"2020","unstructured":"Zeng N, Yan ZP, Chen XY, Ni GX. Infrapatellar fat pad and knee osteoarthritis. Aging Dis. 2020;11:1317\u201328.","journal-title":"Aging Dis"},{"key":"940_CR7","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.14336\/AD.2019.1127","volume":"11","author":"S An","year":"2020","unstructured":"An S, Hu H, Li Y, Hu Y. Pyroptosis plays a role in osteoarthritis. Aging Dis. 2020;11:1146\u201357.","journal-title":"Aging Dis"},{"key":"940_CR8","doi-asserted-by":"publisher","first-page":"567813","DOI":"10.3389\/fcell.2020.567813","volume":"8","author":"M Najar","year":"2020","unstructured":"Najar M, Martel-Pelletier J, Pelletier JP, Fahmi H. Mesenchymal stromal cell immunology for efficient and safe treatment of osteoarthritis. Front Cell Dev Biol. 2020;8:567813.","journal-title":"Front Cell Dev Biol"},{"key":"940_CR9","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13287-021-02138-7","volume":"12","author":"Y Tang","year":"2021","unstructured":"Tang Y, Zhou Y, Li HJ. Advances in mesenchymal stem cell exosomes: a review. Stem Cell Res Ther. 2021;12:71.","journal-title":"Stem Cell Res Ther"},{"key":"940_CR10","doi-asserted-by":"publisher","first-page":"2001689","DOI":"10.1002\/adhm.202001689","volume":"10","author":"C Chang","year":"2021","unstructured":"Chang C, Yan J, Yao Z, Zhang C, Li X, Mao HQ. Effects of mesenchymal stem cell-derived paracrine signals and their delivery strategies. Adv Healthc Mater. 2021;10:2001689.","journal-title":"Adv Healthc Mater"},{"key":"940_CR11","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s13287-020-01957-4","volume":"12","author":"Z Xiao","year":"2021","unstructured":"Xiao Z, Lei T, Liu Y, Yang Y, Bi W, Du H. The potential therapy with dental tissue-derived mesenchymal stem cells in Parkinson\u2019s disease. Stem Cell Res Ther. 2021;12:5.","journal-title":"Stem Cell Res Ther"},{"issue":"4","key":"940_CR12","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1039\/D0BM01164A","volume":"9","author":"M Wang","year":"2020","unstructured":"Wang M, Xin Y, Cao H, Li W, Hua Y, Webster TJ, et al. Recent advances in mesenchymal stem cell membrane-coated nanoparticles for enhanced drug delivery. Biomater Sci. 2020;9(4):1088\u2013103.","journal-title":"Biomater Sci"},{"key":"940_CR13","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1186\/s13287-020-02011-z","volume":"11","author":"Q Xie","year":"2020","unstructured":"Xie Q, Liu R, Jiang J, Peng J, Yang C, Zhang W, et al. What is the impact of human umbilical cord mesenchymal stem cell transplantation on clinical treatment? Stem Cell Res Ther. 2020;11:519.","journal-title":"Stem Cell Res Ther"},{"key":"940_CR14","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1186\/s13287-020-02001-1","volume":"11","author":"P Kangari","year":"2020","unstructured":"Kangari P, Talaei-Khozani T, Razeghian-Jahromi I, Razmkhah M. Mesenchymal stem cells: amazing remedies for bone and cartilage defects. Stem Cell Res Ther. 2020;11:492.","journal-title":"Stem Cell Res Ther"},{"key":"940_CR15","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13018-017-0534-y","volume":"12","author":"A Goldberg","year":"2017","unstructured":"Goldberg A, Mitchell K, Soans J, Kim L, Zaidi R. The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review. J Orthop Surg Res. 2017;12:39.","journal-title":"J Orthop Surg Res"},{"key":"940_CR16","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.pharmthera.2015.02.003","volume":"151","author":"J Kim","year":"2015","unstructured":"Kim J, Shapiro L, Flynn A. The clinical application of mesenchymal stem cells and cardiac stem cells as a therapy for cardiovascular disease. Pharmacol Ther. 2015;151:8\u201315.","journal-title":"Pharmacol Ther"},{"key":"940_CR17","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s12974-019-1571-8","volume":"16","author":"S Dabrowska","year":"2019","unstructured":"Dabrowska S, Andrzejewska A, Lukomska B, Janowski M. Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles. J Neuroinflammation. 2019;16:178.","journal-title":"J Neuroinflammation"},{"key":"940_CR18","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13287-019-1545-x","volume":"11","author":"J Gu","year":"2020","unstructured":"Gu J, Huang L, Zhang C, Wang Y, Zhang R, Tu Z, et al. Therapeutic evidence of umbilical cord-derived mesenchymal stem cell transplantation for cerebral palsy: a randomized, controlled trial. Stem Cell Res Ther. 2020;11:43.","journal-title":"Stem Cell Res Ther"},{"key":"940_CR19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2174\/1872213X14666200130100236","volume":"14","author":"MB Gugjoo","year":"2020","unstructured":"Gugjoo MB, Hussain S, Shah RA, Dhama K. Mesenchymal stem cell-mediated immuno-modulatory and anti- inflammatory mechanisms in immune and allergic disorders. Recent Pat Inflamm Allergy Drug Discov. 2020;14:3\u201314.","journal-title":"Recent Pat Inflamm Allergy Drug Discov"},{"key":"940_CR20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41536-018-0041-8","volume":"3","author":"H Iijima","year":"2018","unstructured":"Iijima H, Isho T, Kuroki H, Takahashi M, Aoyama T. Effectiveness of mesenchymal stem cells for treating patients with knee osteoarthritis: a meta-analysis toward the establishment of effective regenerative rehabilitation. NPJ Regen Med. 2018;3:15.","journal-title":"NPJ Regen Med"},{"key":"940_CR21","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1177\/0363546519899923","volume":"48","author":"JR Garza","year":"2020","unstructured":"Garza JR, Campbell RE, Tjoumakaris FP, Freedman KB, Miller LS, Santa Maria D, et al. Clinical efficacy of intra-articular mesenchymal stromal cells for the treatment of knee osteoarthritis: a double-blinded prospective randomized controlled clinical trial. Am J Sports Med. 2020;48:588\u201398.","journal-title":"Am J Sports Med"},{"key":"940_CR22","doi-asserted-by":"publisher","first-page":"3342","DOI":"10.1007\/s00167-018-4883-9","volume":"26","author":"R Bastos","year":"2018","unstructured":"Bastos R, Mathias M, Andrade R, Bastos R, Balduino A, Schott V, et al. Intra-articular injections of expanded mesenchymal stem cells with and without addition of platelet-rich plasma are safe and effective for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2018;26:3342\u201350.","journal-title":"Knee Surg Sports Traumatol Arthrosc"},{"key":"940_CR23","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1089\/scd.2011.0670","volume":"21","author":"V Dexheimer","year":"2012","unstructured":"Dexheimer V, Frank S, Richter W. Proliferation as a requirement for in vitro chondrogenesis of human mesenchymal stem cells. Stem Cells Dev. 2012;21:2160\u20139.","journal-title":"Stem Cells Dev"},{"key":"940_CR24","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1634\/stemcells.2004-0062","volume":"22","author":"BC Heng","year":"2004","unstructured":"Heng BC, Cao T, Lee EH. Directing stem cell differentiation into the chondrogenic lineage in vitro. Stem Cells. 2004;22:1152\u201367.","journal-title":"Stem Cells"},{"key":"940_CR25","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1016\/j.joca.2015.07.004","volume":"23","author":"YM Pers","year":"2015","unstructured":"Pers YM, Ruiz M, Noel D, Jorgensen C. Mesenchymal stem cells for the management of inflammation in osteoarthritis: state of the art and perspectives. Osteoarthr Cartil. 2015;23:2027\u201335.","journal-title":"Osteoarthr Cartil"},{"key":"940_CR26","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1517\/14712598.2016.1093108","volume":"16","author":"M Ruiz","year":"2016","unstructured":"Ruiz M, Cosenza S, Maumus M, Jorgensen C, Noel D. Therapeutic application of mesenchymal stem cells in osteoarthritis. Expert Opin Biol Ther. 2016;16:33\u201342.","journal-title":"Expert Opin Biol Ther"},{"key":"940_CR27","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1038\/ni.3002","volume":"15","author":"Y Wang","year":"2014","unstructured":"Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014;15:1009\u201316.","journal-title":"Nat Immunol"},{"key":"940_CR28","doi-asserted-by":"publisher","first-page":"732742","DOI":"10.1155\/2013\/732742","volume":"2013","author":"TJ Kean","year":"2013","unstructured":"Kean TJ, Lin P, Caplan AI, Dennis JE. MSCs: delivery routes and engraftment, cell-targeting strategies, and immune modulation. Stem Cells Int. 2013;2013:732742.","journal-title":"Stem Cells Int."},{"key":"940_CR29","doi-asserted-by":"publisher","first-page":"3057624","DOI":"10.1155\/2018\/3057624","volume":"2018","author":"M Wang","year":"2018","unstructured":"Wang M, Yuan Q, Xie L. Mesenchymal stem cell-based immunomodulation: properties and clinical application. Stem Cells Int. 2018;2018:3057624.","journal-title":"Stem Cells Int"},{"key":"940_CR30","doi-asserted-by":"publisher","first-page":"110173","DOI":"10.1016\/j.micromeso.2020.110173","volume":"300","author":"HN Abdelhamid","year":"2020","unstructured":"Abdelhamid HN, Dowaidar M, Hallbrink M, Langel U. Gene delivery using cell penetrating peptides-zeolitic imidazolate frameworks. Micropor Mesopor Mat. 2020;300:110173.","journal-title":"Micropor Mesopor Mat"},{"key":"940_CR31","doi-asserted-by":"publisher","first-page":"110200","DOI":"10.1016\/j.micromeso.2020.110200","volume":"302","author":"HN Abdelhamid","year":"2020","unstructured":"Abdelhamid HN, Dowaidar M, Langel U. Carbonized chitosan encapsulated hierarchical porous zeolitic imidazolate frameworks nanoparticles for gene delivery. Micropor Mesopor Mat. 2020;302:110200.","journal-title":"Micropor Mesopor Mat."},{"key":"940_CR32","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s13287-021-02161-8","volume":"12","author":"L Liang","year":"2021","unstructured":"Liang L, Zheng D, Lu C, Xi Q, Bao H, Li W, et al. Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models. Stem Cell Res Ther. 2021;12:87.","journal-title":"Stem Cell Res Ther"},{"key":"940_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.03.020","author":"BH Sung","year":"2021","unstructured":"Sung BH, Parent CA, Weaver AM. Extracellular vesicles: Critical players during cell migration. Dev Cell. 2021. https:\/\/doi.org\/10.1016\/j.devcel.2021.03.020.","journal-title":"Dev Cell"},{"key":"940_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.03.032","author":"A Yokoi","year":"2021","unstructured":"Yokoi A, Ochiya T. Exosomes and extracellular vesicles: rethinking the essential values in cancer biology. Semin Cancer Biol. 2021. https:\/\/doi.org\/10.1016\/j.semcancer.2021.03.032.","journal-title":"Semin Cancer Biol"},{"key":"940_CR35","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.addr.2021.03.005","volume":"173","author":"M Schulz-Siegmund","year":"2021","unstructured":"Schulz-Siegmund M, Aigner A. Nucleic acid delivery with extracellular vesicles. Adv Drug Deliv Rev. 2021;173:89\u2013111.","journal-title":"Adv Drug Deliv Rev"},{"key":"940_CR36","doi-asserted-by":"publisher","first-page":"e12033","DOI":"10.1002\/jev2.12033","volume":"10","author":"VVT Nguyen","year":"2020","unstructured":"Nguyen VVT, Witwer KW, Verhaar MC, Strunk D, van Balkom BWM. Functional assays to assess the therapeutic potential of extracellular vesicles. J Extracell Vesicles. 2020;10:e12033.","journal-title":"J Extracell Vesicles"},{"key":"940_CR37","doi-asserted-by":"publisher","first-page":"e255","DOI":"10.1002\/ctm2.255","volume":"11","author":"L Yan","year":"2021","unstructured":"Yan L, Liu G, Wu X. The umbilical cord mesenchymal stem cell-derived exosomal lncRNA H19 improves osteochondral activity through miR-29b-3p\/FoxO3 axis. Clin Transl Med. 2021;11:e255.","journal-title":"Clin Transl Med"},{"issue":"1","key":"940_CR38","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s00441-020-03319-1","volume":"384","author":"R Wang","year":"2021","unstructured":"Wang R, Xu B. TGF-beta1-modified MSC-derived exosomal miR-135b attenuates cartilage injury via promoting M2 synovial macrophage polarization by targeting MAPK6. Cell Tissue Res. 2021;384(1):113\u201327.","journal-title":"Cell Tissue Res"},{"key":"940_CR39","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1016\/j.joca.2016.06.022","volume":"24","author":"S Zhang","year":"2016","unstructured":"Zhang S, Chu WC, Lai RC, Lim SK, Hui JH, Toh WS. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthr Cartil. 2016;24:2135\u201340.","journal-title":"Osteoarthr Cartil"},{"key":"940_CR40","doi-asserted-by":"publisher","first-page":"16214","DOI":"10.1038\/s41598-017-15376-8","volume":"7","author":"S Cosenza","year":"2017","unstructured":"Cosenza S, Ruiz M, Toupet K, Jorgensen C, Noel D. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci Rep. 2017;7:16214.","journal-title":"Sci Rep"},{"key":"940_CR41","doi-asserted-by":"publisher","first-page":"2755","DOI":"10.7150\/thno.56174","volume":"11","author":"Z Rong","year":"2021","unstructured":"Rong Z, Xu J, Shi S, Tan Z, Meng Q, Hua J, et al. Circular RNA in pancreatic cancer: a novel avenue for the roles of diagnosis and treatment. Theranostics. 2021;11:2755\u201369.","journal-title":"Theranostics"},{"key":"940_CR42","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.omtn.2020.11.008","volume":"23","author":"T Shao","year":"2021","unstructured":"Shao T, Pan YH, Xiong XD. Circular RNA: an important player with multiple facets to regulate its parental gene expression. Mol Ther Nucleic Acids. 2021;23:369\u201376.","journal-title":"Mol Ther Nucleic Acids"},{"key":"940_CR43","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.14336\/AD.2020.0309","volume":"11","author":"YH Pan","year":"2020","unstructured":"Pan YH, Wu WP, Xiong XD. Circular RNAs: Promising biomarkers for age-related diseases. Aging Dis. 2020;11:1585\u201393.","journal-title":"Aging Dis"},{"key":"940_CR44","doi-asserted-by":"publisher","first-page":"568366","DOI":"10.3389\/fcell.2020.568366","volume":"8","author":"T Seimiya","year":"2020","unstructured":"Seimiya T, Otsuka M, Iwata T, Shibata C, Tanaka E, Suzuki T, et al. Emerging roles of exosomal circular RNAs in cancer. Front Cell Dev Biol. 2020;8:568366.","journal-title":"Front Cell Dev Biol"},{"key":"940_CR45","doi-asserted-by":"publisher","first-page":"e1633","DOI":"10.1002\/wrna.1633","volume":"12","author":"D Tsitsipatis","year":"2021","unstructured":"Tsitsipatis D, Gorospe M. Practical guide for circular RNA analysis: Steps, tips, and resources. Wiley Interdiscip Rev RNA. 2021;12:e1633.","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"940_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.semcdb.2020.08.003","volume":"114","author":"BS Guerra","year":"2020","unstructured":"Guerra BS, Lima J, Araujo B, Torres LB, Santos J, Machado D, et al. Biogenesis of circular RNAs and their role in cellular and molecular phenotypes of neurological disorders. Semin Cell Dev Biol. 2020;114:1\u201310.","journal-title":"Semin Cell Dev Biol"},{"issue":"9","key":"940_CR47","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.3390\/cancers12092464","volume":"12","author":"PI Artemaki","year":"2020","unstructured":"Artemaki PI, Scorilas A, Kontos CK. Circular RNAs: a new piece in the colorectal cancer puzzle. Cancers (Basel). 2020;12(9):2464.","journal-title":"Cancers (Basel)."},{"key":"940_CR48","doi-asserted-by":"publisher","first-page":"7954657","DOI":"10.1155\/2019\/7954657","volume":"2019","author":"Y Wang","year":"2019","unstructured":"Wang Y, Zhao R, Liu W, Wang Z, Rong J, Long X, et al. Exosomal circHIPK3 released from hypoxia-pretreated cardiomyocytes regulates oxidative damage in cardiac microvascular endothelial cells via the miR-29a\/IGF-1 pathway. Oxid Med Cell Longev. 2019;2019:7954657.","journal-title":"Oxid Med Cell Longev"},{"key":"940_CR49","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1080\/15548627.2019.1634945","volume":"16","author":"X Chen","year":"2020","unstructured":"Chen X, Mao R, Su W, Yang X, Geng Q, Guo C, et al. Circular RNA circHIPK3 modulates autophagy via MIR124-3p-STAT3-PRKAA\/AMPKalpha signaling in STK11 mutant lung cancer. Autophagy. 2020;16:659\u201371.","journal-title":"Autophagy"},{"key":"940_CR50","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/s41419-019-1430-7","volume":"10","author":"JX Zhang","year":"2019","unstructured":"Zhang JX, Lu J, Xie H, Wang DP, Ni HE, Zhu Y, et al. circHIPK3 regulates lung fibroblast-to-myofibroblast transition by functioning as a competing endogenous RNA. Cell Death Dis. 2019;10:182.","journal-title":"Cell Death Dis"},{"key":"940_CR51","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s41419-017-0204-3","volume":"9","author":"G Chen","year":"2018","unstructured":"Chen G, Shi Y, Liu M, Sun J. circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in hepatocellular carcinoma. Cell Death Dis. 2018;9:175.","journal-title":"Cell Death Dis"},{"key":"940_CR52","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.15252\/embr.201643581","volume":"18","author":"Y Li","year":"2017","unstructured":"Li Y, Zheng F, Xiao X, Xie F, Tao D, Huang C, et al. CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells. EMBO Rep. 2017;18:1646\u201359.","journal-title":"EMBO Rep"},{"key":"940_CR53","doi-asserted-by":"publisher","first-page":"11215","DOI":"10.1038\/ncomms11215","volume":"7","author":"Q Zheng","year":"2016","unstructured":"Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016;7:11215.","journal-title":"Nat Commun"},{"issue":"2","key":"940_CR54","doi-asserted-by":"publisher","first-page":"177","DOI":"10.3390\/cells8020177","volume":"8","author":"B Chen","year":"2019","unstructured":"Chen B, Yu J, Guo L, Byers MS, Wang Z, Chen X, et al. Circular RNA circHIPK3 promotes the proliferation and differentiation of chicken myoblast cells by sponging miR-30a-3p. Cells. 2019;8(2):177.","journal-title":"Cells"},{"key":"940_CR55","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.18632\/aging.102674","volume":"12","author":"J Liang","year":"2020","unstructured":"Liang J, Shen YC, Zhang XY, Chen C, Zhao H, Hu J. Circular RNA HIPK3 downregulation mediates hydrogen peroxide-induced cytotoxicity in human osteoblasts. Aging (Albany NY). 2020;12:1159\u201370.","journal-title":"Aging (Albany NY)"},{"key":"940_CR56","doi-asserted-by":"publisher","first-page":"6630","DOI":"10.18632\/aging.103003","volume":"12","author":"YS Chiu","year":"2020","unstructured":"Chiu YS, Wu JL, Yeh CT, Yadav VK, Huang HS, Wang LS. gamma-Mangostin isolated from Garcinia mangostana L. suppresses inflammation and alleviates symptoms of osteoarthritis via modulating miR-124-3p\/IL-6\/NF-kappaB signaling. Aging (Albany NY). 2020;12:6630\u201343.","journal-title":"Aging (Albany NY)"},{"key":"940_CR57","doi-asserted-by":"publisher","first-page":"213","DOI":"10.2217\/rme-2018-0161","volume":"14","author":"J Freitag","year":"2019","unstructured":"Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A, et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med. 2019;14:213\u201330.","journal-title":"Regen Med"},{"key":"940_CR58","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s11926-018-0776-7","volume":"20","author":"CDS Ranmuthu","year":"2018","unstructured":"Ranmuthu CDS, Ranmuthu CKI, Khan WS. Evaluating the current literature on treatments containing adipose-derived stem cells for osteoarthritis: a progress update. Curr Rheumatol Rep. 2018;20:67.","journal-title":"Curr Rheumatol Rep"},{"key":"940_CR59","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1097\/01.NAJ.0000580260.18537.ca","volume":"119","author":"E Draganski","year":"2019","unstructured":"Draganski E, Deason T, Craig FE. Bone marrow aspiration and biopsy performed by RNs: a review of clinical practice. Am J Nurs. 2019;119:47\u201353.","journal-title":"Am J Nurs"},{"key":"940_CR60","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.gde.2020.12.018","volume":"66","author":"K Stefanius","year":"2021","unstructured":"Stefanius K, Servage K, Orth K. Exosomes in cancer development. Curr Opin Genet Dev. 2021;66:83\u201392.","journal-title":"Curr Opin Genet Dev"},{"issue":"1","key":"940_CR61","doi-asserted-by":"publisher","first-page":"84","DOI":"10.3390\/cancers13010084","volume":"13","author":"H Aheget","year":"2021","unstructured":"Aheget H, Mazini L, Martin F, Belqat B, Marchal JA, Benabdellah K. Exosomes: their role in pathogenesis, diagnosis and treatment of diseases. Cancers (Basel). 2021;13(1):84.","journal-title":"Cancers (Basel)"},{"key":"940_CR62","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.7150\/thno.53326","volume":"11","author":"YY Xiong","year":"2021","unstructured":"Xiong YY, Gong ZT, Tang RJ, Yang YJ. The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction. Theranostics. 2021;11:1046\u201358.","journal-title":"Theranostics"},{"key":"940_CR63","doi-asserted-by":"publisher","first-page":"110319","DOI":"10.1016\/j.ecoenv.2020.110319","volume":"193","author":"Q Guan","year":"2020","unstructured":"Guan Q, Chen S, Wang B, Dou X, Lu Y, Liang J, et al. Effects of particulate matter exposure on semen quality: a retrospective cohort study. Ecotoxicol Environ Saf. 2020;193:110319.","journal-title":"Ecotoxicol Environ Saf"},{"key":"940_CR64","doi-asserted-by":"publisher","DOI":"10.1007\/s13770-020-00324-x","author":"M Kim","year":"2021","unstructured":"Kim M, Shin DI, Choi BH, Min BH. Exosomes from IL-1beta-primed mesenchymal stem cells inhibited IL-1beta- and TNF-alpha-mediated inflammatory responses in osteoarthritic SW982 cells. Tissue Eng Regen Med. 2021. https:\/\/doi.org\/10.1007\/s13770-020-00324-x.","journal-title":"Tissue Eng Regen Med"},{"key":"940_CR65","doi-asserted-by":"publisher","first-page":"118987","DOI":"10.1016\/j.lfs.2020.118987","volume":"269","author":"M Qiu","year":"2021","unstructured":"Qiu M, Liu D, Fu Q. MiR-129-5p shuttled by human synovial mesenchymal stem cell-derived exosomes relieves IL-1beta induced osteoarthritis via targeting HMGB1. Life Sci. 2021;269:118987.","journal-title":"Life Sci"},{"key":"940_CR66","doi-asserted-by":"publisher","first-page":"575057","DOI":"10.3389\/fbioe.2020.575057","volume":"8","author":"X Zhao","year":"2020","unstructured":"Zhao X, Zhao Y, Sun X, Xing Y, Wang X, Yang Q. Immunomodulation of MSCs and MSC-derived extracellular vesicles in osteoarthritis. Front Bioeng Biotechnol. 2020;8:575057.","journal-title":"Front Bioeng Biotechnol"},{"key":"940_CR67","doi-asserted-by":"publisher","first-page":"10855","DOI":"10.1111\/jcmm.15714","volume":"24","author":"B Qiu","year":"2020","unstructured":"Qiu B, Xu X, Yi P, Hao Y. Curcumin reinforces MSC-derived exosomes in attenuating osteoarthritis via modulating the miR-124\/NF-kB and miR-143\/ROCK1\/TLR9 signalling pathways. J Cell Mol Med. 2020;24:10855\u201365.","journal-title":"J Cell Mol Med"},{"key":"940_CR68","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00441-020-03193-x","volume":"381","author":"Z Jin","year":"2020","unstructured":"Jin Z, Ren J, Qi S. Exosomal miR-9-5p secreted by bone marrow-derived mesenchymal stem cells alleviates osteoarthritis by inhibiting syndecan-1. Cell Tissue Res. 2020;381:99\u2013114.","journal-title":"Cell Tissue Res"},{"key":"940_CR69","doi-asserted-by":"publisher","first-page":"105946","DOI":"10.1016\/j.intimp.2019.105946","volume":"78","author":"Z Jin","year":"2020","unstructured":"Jin Z, Ren J, Qi S. Human bone mesenchymal stem cells-derived exosomes overexpressing microRNA-26a-5p alleviate osteoarthritis via down-regulation of PTGS2. Int Immunopharmacol. 2020;78:105946.","journal-title":"Int Immunopharmacol"},{"key":"940_CR70","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1161\/CIRCULATIONAHA.120.049715","volume":"143","author":"Z Zeng","year":"2021","unstructured":"Zeng Z, Xia L, Fan S, Zheng J, Qin J, Fan X, et al. Circular RNA CircMAP3K5 acts as a MicroRNA-22-3p sponge to promote resolution of intimal hyperplasia via TET2-mediated smooth muscle cell differentiation. Circulation. 2021;143:354\u201371.","journal-title":"Circulation"},{"key":"940_CR71","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/s41580-020-0243-y","volume":"21","author":"LL Chen","year":"2020","unstructured":"Chen LL. The expanding regulatory mechanisms and cellular functions of circular RNAs. Nat Rev Mol Cell Biol. 2020;21:475\u201390.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"940_CR72","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/s41576-019-0158-7","volume":"20","author":"LS Kristensen","year":"2019","unstructured":"Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20:675\u201391.","journal-title":"Nat Rev Genet"},{"key":"940_CR73","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s12935-020-01743-5","volume":"21","author":"B Zhu","year":"2021","unstructured":"Zhu B, Cui H, Xu W. Hydrogen inhibits the proliferation and migration of gastric cancer cells by modulating lncRNA MALAT1\/miR-124-3p\/EZH2 axis. Cancer Cell Int. 2021;21:70.","journal-title":"Cancer Cell Int"},{"key":"940_CR74","doi-asserted-by":"publisher","first-page":"668","DOI":"10.3892\/ijmm.2020.4804","volume":"47","author":"X Yang","year":"2021","unstructured":"Yang X, Wang J, Li H, Sun Y, Tong X. Downregulation of hsa_circ_0026123 suppresses ovarian cancer cell metastasis and proliferation through the miR1243p\/EZH2 signaling pathway. Int J Mol Med. 2021;47:668\u201376.","journal-title":"Int J Mol Med"},{"key":"940_CR75","first-page":"4372","volume":"10","author":"J Sha","year":"2020","unstructured":"Sha J, Xia L, Han Q, Chi C, Zhu Y, Pan J, et al. Downregulation of circ-TRPS1 suppressed prostatic cancer prognoses by regulating miR-124-3p\/EZH2 axis-mediated stemness. Am J Cancer Res. 2020;10:4372\u201385.","journal-title":"Am J Cancer Res"},{"key":"940_CR76","doi-asserted-by":"publisher","first-page":"119143","DOI":"10.1016\/j.lfs.2021.119143","volume":"270","author":"B Wang","year":"2021","unstructured":"Wang B, Li J, Tian F. Downregulation of lncRNA SNHG14 attenuates osteoarthritis by inhibiting FSTL-1 mediated NLRP3 and TLR4\/NF-kappaB pathway through miR-124\u20133p. Life Sci. 2021;270:119143.","journal-title":"Life Sci"},{"key":"940_CR77","doi-asserted-by":"publisher","first-page":"4046","DOI":"10.1080\/21691401.2019.1673765","volume":"47","author":"H Ni","year":"2019","unstructured":"Ni H, Wang G, Xu Y, Gu X, Sun C, Li H. Lycium barbarum polysaccharide alleviates IL-1beta-evoked chondrogenic ATDC5 cell inflammatory injury through mediation of microRNA-124. Artif Cells Nanomed Biotechnol. 2019;47:4046\u201352.","journal-title":"Artif Cells Nanomed Biotechnol"},{"key":"940_CR78","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1158\/0008-5472.CAN-20-1010","volume":"81","author":"Y Hu","year":"2021","unstructured":"Hu Y, Yang C, Amorim T, Maqbool M, Lin J, Li C, et al. Cisplatin-mediated upregulation of APE2 binding to MYH9 provokes mitochondrial fragmentation and acute kidney injury. Cancer Res. 2021;81:713\u201323.","journal-title":"Cancer Res"},{"key":"940_CR79","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.138530","author":"KL Otterpohl","year":"2020","unstructured":"Otterpohl KL, Busselman BW, Ratnayake I, Hart RG, Hart KR, Evans CM, et al. Conditional Myh9 and Myh10 inactivation in adult mouse renal epithelium results in progressive kidney disease. JCI Insight. 2020. https:\/\/doi.org\/10.1172\/jci.insight.138530.","journal-title":"JCI Insight."},{"key":"940_CR80","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1681\/ASN.2015060707","volume":"29","author":"S Cechova","year":"2018","unstructured":"Cechova S, Dong F, Chan F, Kelley MJ, Ruiz P, Le TH. MYH9 E1841K mutation augments proteinuria and podocyte injury and migration. J Am Soc Nephrol. 2018;29:155\u201367.","journal-title":"J Am Soc Nephrol"},{"key":"940_CR81","doi-asserted-by":"publisher","first-page":"535","DOI":"10.3389\/fendo.2020.00535","volume":"11","author":"ST Yu","year":"2020","unstructured":"Yu ST, Sun BH, Ge JN, Shi JL, Zhu MS, Wei ZG, et al. CRLF1-MYH9 interaction regulates proliferation and metastasis of papillary thyroid carcinoma through the ERK\/ETV4 axis. Front Endocrinol (Lausanne). 2020;11:535.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"940_CR82","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1080\/21655979.2020.1863014","volume":"12","author":"H Zhang","year":"2021","unstructured":"Zhang H, Liu S, Tang L, Ge J, Lu X. Long non-coding RNA (LncRNA) MRPL23-AS1 promotes tumor progression and carcinogenesis in osteosarcoma by activating Wnt\/beta-catenin signaling via inhibiting microRNA miR-30b and upregulating myosin heavy chain 9 (MYH9). Bioengineered. 2021;12:162\u201371.","journal-title":"Bioengineered"},{"key":"940_CR83","doi-asserted-by":"publisher","first-page":"7545","DOI":"10.7150\/thno.46001","volume":"10","author":"G Ye","year":"2020","unstructured":"Ye G, Yang Q, Lei X, Zhu X, Li F, He J, et al. Nuclear MYH9-induced CTNNB1 transcription, targeted by staurosporin, promotes gastric cancer cell anoikis resistance and metastasis. Theranostics. 2020;10:7545\u201360.","journal-title":"Theranostics"},{"key":"940_CR84","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s12032-020-01413-6","volume":"37","author":"SK Singh","year":"2020","unstructured":"Singh SK, Sinha S, Padhan J, Jangde N, Ray R, Rai V. MYH9 suppresses melanoma tumorigenesis, metastasis and regulates tumor microenvironment. Med Oncol. 2020;37:88.","journal-title":"Med Oncol"},{"key":"940_CR85","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/978-1-4939-2550-6_15","volume":"1295","author":"DW Greening","year":"2015","unstructured":"Greening DW, Xu R, Ji H, Tauro BJ, Simpson RJ. A protocol for exosome isolation and characterization: evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods. Methods Mol Biol. 2015;1295:179\u2013209.","journal-title":"Methods Mol Biol"}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-021-00940-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12951-021-00940-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-021-00940-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T09:03:54Z","timestamp":1675501434000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-021-00940-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,30]]},"references-count":85,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["940"],"URL":"https:\/\/doi.org\/10.1186\/s12951-021-00940-2","relation":{},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,30]]},"assertion":[{"value":"15 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal study was reviewed and approved by the Animal Care and Use Committee of China Medical University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"194"}}