{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:29:51Z","timestamp":1793824191171,"version":"4.6.1"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council of Singapore","doi-asserted-by":"crossref","award":["MOH-000371-00"],"award-info":[{"award-number":["MOH-000371-00"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["23ZR1451700"],"award-info":[{"award-number":["23ZR1451700"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical-Engineering Cross Project of Shanghai Jiao Tong University","award":["YG2022QN076"],"award-info":[{"award-number":["YG2022QN076"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"DOI":"10.1186\/s13287-025-04412-4","type":"journal-article","created":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T13:51:32Z","timestamp":1749304292000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism"],"prefix":"10.1186","volume":"16","author":[{"given":"Haifeng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingnan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinitha","family":"Denslin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Wei Justin","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhai","family":"Zhuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing Moon Raymond","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinxian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Hoi Po","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4275-0590","authenticated-orcid":false,"given":"Zheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"issue":"6","key":"4412_CR1","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1001\/jama.2020.22171","volume":"325","author":"JN Katz","year":"2021","unstructured":"Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA. 2021;325(6):568\u201378.","journal-title":"JAMA"},{"issue":"2","key":"4412_CR2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.joca.2020.10.006","volume":"29","author":"MH van den Bosch","year":"2021","unstructured":"van den Bosch MH. Osteoarthritis year in review 2020: biology. Osteoarthr Cartil. 2021;29(2):143\u201350.","journal-title":"Osteoarthr Cartil"},{"issue":"2","key":"4412_CR3","first-page":"293","volume":"104","author":"B Abramoff","year":"2020","unstructured":"Abramoff B, Caldera FE. Osteoarthritis: pathology, diagnosis, and treatment options. Med Clin. 2020;104(2):293\u2013311.","journal-title":"Med Clin"},{"issue":"17","key":"4412_CR4","doi-asserted-by":"publisher","first-page":"9208","DOI":"10.3390\/ijms22179208","volume":"22","author":"V Molnar","year":"2021","unstructured":"Molnar V, Mati\u0161i\u0107 V, Kodvanj I, Bjelica R, Jele\u010d \u017d, Hudetz D, et al. Cytokines and chemokines involved in osteoarthritis pathogenesis. Int J Mol Sci. 2021;22(17):9208.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"4412_CR5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1177\/0036933015619588","volume":"61","author":"S Hussain","year":"2016","unstructured":"Hussain S, Neilly D, Baliga S, Patil S, Meek R. Knee osteoarthritis: a review of management options. Scott Med J. 2016;61(1):7\u201316.","journal-title":"Scott Med J"},{"issue":"1","key":"4412_CR6","doi-asserted-by":"publisher","first-page":"2984","DOI":"10.1080\/21655979.2021.1943602","volume":"12","author":"Y Tang","year":"2021","unstructured":"Tang Y, Li Y, Xin D, Chen L, Xiong Z, Yu X. Icariin alleviates osteoarthritis by regulating autophagy of chondrocytes by mediating PI3K\/AKT\/mTOR signaling. Bioengineered. 2021;12(1):2984\u201399.","journal-title":"Bioengineered"},{"issue":"4","key":"4412_CR7","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1136\/annrheumdis-2011-200557","volume":"71","author":"B Caram\u00e9s","year":"2012","unstructured":"Caram\u00e9s B, Hasegawa A, Taniguchi N, Miyaki S, Blanco FJ, Lotz M. Autophagy activation by Rapamycin reduces severity of experimental osteoarthritis. Ann Rheum Dis. 2012;71(4):575\u201381.","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"4412_CR8","doi-asserted-by":"publisher","first-page":"5781660","DOI":"10.1155\/2022\/5781660","volume":"2022","author":"Z Deng","year":"2022","unstructured":"Deng Z, Long D, Liu H, Xu Y, Xin R, Liao H, et al. tRNA-Derived fragment tRF\u20105009A regulates autophagy and degeneration of cartilage in osteoarthritis via targeting mTOR. Oxid Med Cell Longev. 2022;2022(1):5781660.","journal-title":"Oxid Med Cell Longev"},{"issue":"6","key":"4412_CR9","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/s41576-022-00562-w","volume":"24","author":"H Yamamoto","year":"2023","unstructured":"Yamamoto H, Zhang S, Mizushima N. Autophagy genes in biology and disease. Nat Rev Genet. 2023;24(6):382\u2013400.","journal-title":"Nat Rev Genet"},{"issue":"1","key":"4412_CR10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/path.2697","volume":"221","author":"D Glick","year":"2010","unstructured":"Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010;221(1):3\u201312.","journal-title":"J Pathol"},{"issue":"19","key":"4412_CR11","doi-asserted-by":"publisher","first-page":"e108863","DOI":"10.15252\/embj.2021108863","volume":"40","author":"DJ Klionsky","year":"2021","unstructured":"Klionsky DJ, Petroni G, Amaravadi RK, Baehrecke EH, Ballabio A, Boya P, et al. Autophagy in major human diseases. EMBO. 2021;40(19):e108863.","journal-title":"EMBO"},{"issue":"11","key":"4412_CR12","doi-asserted-by":"publisher","first-page":"2887","DOI":"10.3390\/cells10112887","volume":"10","author":"TH Nguyen","year":"2021","unstructured":"Nguyen TH, Duong CM, Nguyen X-H, Than UTT. Mesenchymal stem cell-derived extracellular vesicles for osteoarthritis treatment: extracellular matrix protection, chondrocyte and osteocyte physiology, pain and inflammation management. Cells. 2021;10(11):2887.","journal-title":"Cells"},{"issue":"1","key":"4412_CR13","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41413-020-0100-9","volume":"8","author":"Z Ni","year":"2020","unstructured":"Ni Z, Zhou S, Li S, Kuang L, Chen H, Luo X, et al. Exosomes: roles and therapeutic potential in osteoarthritis. Bone Res. 2020;8(1):25.","journal-title":"Bone Res"},{"key":"4412_CR14","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.biomaterials.2019.03.022","volume":"206","author":"J Wu","year":"2019","unstructured":"Wu J, Kuang L, Chen C, Yang J, Zeng W-N, Li T, et al. miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via Inhibition of mTOR in osteoarthritis. Biomaterials. 2019;206:87\u2013100.","journal-title":"Biomaterials"},{"issue":"3","key":"4412_CR15","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1080\/15384101.2021.2019411","volume":"21","author":"C Wen","year":"2022","unstructured":"Wen C, Lin L, Zou R, Lin F, Liu Y. Mesenchymal stem cell-derived exosome mediated long non-coding RNA KLF3-AS1 represses autophagy and apoptosis of chondrocytes in osteoarthritis. Cell Cycle. 2022;21(3):289\u2013303.","journal-title":"Cell Cycle"},{"issue":"1","key":"4412_CR16","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1186\/s12951-023-02264-9","volume":"21","author":"C Lou","year":"2023","unstructured":"Lou C, Jiang H, Lin Z, Xia T, Wang W, Lin C, et al. MiR-146b-5p enriched bioinspired exosomes derived from fucoidan-directed induction mesenchymal stem cells protect chondrocytes in osteoarthritis by targeting TRAF6. J Nanobiotechnol. 2023;21(1):486.","journal-title":"J Nanobiotechnol"},{"key":"4412_CR17","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.bioactmat.2023.03.017","volume":"27","author":"Y Yang","year":"2023","unstructured":"Yang Y, Wu Y, Yang D, Neo SH, Kadir ND, Goh D, et al. Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles. Bioactive Mater. 2023;27:98\u2013112.","journal-title":"Bioactive Mater"},{"issue":"1","key":"4412_CR18","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12974-020-1726-7","volume":"17","author":"W Liu","year":"2020","unstructured":"Liu W, Rong Y, Wang J, Zhou Z, Ge X, Ji C, et al. Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1\/M2 polarization. J Neuroinflammation. 2020;17(1):47.","journal-title":"J Neuroinflammation"},{"key":"4412_CR19","doi-asserted-by":"crossref","unstructured":"Zhang B, Tian X, Qu Z, Hao J, Zhang W. Hypoxia-Preconditioned extracellular vesicles from mesenchymal stem cells improve cartilage repair in osteoarthritis. Membr (Basel). 2022;12(2).","DOI":"10.3390\/membranes12020225"},{"key":"4412_CR20","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/978-1-60761-987-1_18","volume":"696","author":"M Kohl","year":"2011","unstructured":"Kohl M, Wiese S, Warscheid B. Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol. 2011;696:291\u2013303.","journal-title":"Methods Mol Biol"},{"issue":"5","key":"4412_CR21","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.joca.2004.02.001","volume":"12","author":"T Pham","year":"2004","unstructured":"Pham T, van der Heijde D, Altman R, Anderson J, Bellamy N, Hochberg M, et al. OMERACT-OARSI initiative: osteoarthritis research society international set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthr Cartil. 2004;12(5):389\u201399.","journal-title":"Osteoarthr Cartil"},{"key":"4412_CR22","doi-asserted-by":"publisher","first-page":"105268","DOI":"10.1016\/j.meegid.2022.105268","volume":"100","author":"H Wang","year":"2022","unstructured":"Wang H, Zhang C, Zhang C, Wang Y, Zhai K, Tong Z. MicroRNA-122-5p regulates coagulation and inflammation through MASP1 and HO-1 genes. Infect Genet Evol. 2022;100:105268.","journal-title":"Infect Genet Evol"},{"key":"4412_CR23","unstructured":"Li K-W, Wang S-H, Wei X, Hou Y-Z, Li Z-H. Mechanism of miR-122-5p regulating the activation of PI3K-Akt-mTOR signaling pathway on the cell proliferation and apoptosis of osteosarcoma cells through targeting TP53 gene. Eur Rev Med Pharmacol Sci. 2020;24(24)."},{"issue":"4","key":"4412_CR24","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.cellsig.2015.01.010","volume":"27","author":"K Hamamura","year":"2015","unstructured":"Hamamura K, Nishimura A, Chen A, Takigawa S, Sudo A, Yokota H. Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis. Cell Signal. 2015;27(4):828\u201335.","journal-title":"Cell Signal"},{"key":"4412_CR25","doi-asserted-by":"publisher","first-page":"101864","DOI":"10.1016\/j.arr.2023.101864","volume":"85","author":"B You","year":"2023","unstructured":"You B, Zhou C, Yang Y. MSC-EVs alleviate osteoarthritis by regulating microenvironmental cells in the articular cavity and maintaining cartilage matrix homeostasis. Ageing Res Rev. 2023;85:101864.","journal-title":"Ageing Res Rev"},{"key":"4412_CR26","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.matbio.2017.10.003","volume":"75","author":"K Rilla","year":"2019","unstructured":"Rilla K, Mustonen A-M, Arasu UT, H\u00e4rk\u00f6nen K, Matilainen J, Nieminen P. Extracellular vesicles are integral and functional components of the extracellular matrix. Matrix Biol. 2019;75:201\u201319.","journal-title":"Matrix Biol"},{"key":"4412_CR27","doi-asserted-by":"publisher","first-page":"e935937","DOI":"10.12659\/MSM.935937","volume":"28","author":"S Ren","year":"2022","unstructured":"Ren S, Wang C, Guo S. Review of the role of mesenchymal stem cells and exosomes derived from mesenchymal stem cells in the treatment of orthopedic disease. Med Sci Monitor: Int Med J Experimental Clin Res. 2022;28:e935937\u201311.","journal-title":"Med Sci Monitor: Int Med J Experimental Clin Res"},{"issue":"9","key":"4412_CR28","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1089\/scd.2016.0349","volume":"26","author":"GD Kusuma","year":"2017","unstructured":"Kusuma GD, Carthew J, Lim R, Frith JE. Effect of the microenvironment on mesenchymal stem cell paracrine signaling: opportunities to engineer the therapeutic effect. Stem Cells Dev. 2017;26(9):617\u201331.","journal-title":"Stem Cells Dev"},{"issue":"5","key":"4412_CR29","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1089\/ten.teb.2021.0145","volume":"28","author":"Y Yang","year":"2022","unstructured":"Yang Y, Lee EH, Yang Z. Hypoxia-conditioned mesenchymal stem cells in tissue regeneration application. Tissue Eng Part B: Reviews. 2022;28(5):966\u201377.","journal-title":"Tissue Eng Part B: Reviews"},{"key":"4412_CR30","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.actbio.2022.02.026","volume":"143","author":"K Shen","year":"2022","unstructured":"Shen K, Duan A, Cheng J, Yuan T, Zhou J, Song H, et al. Exosomes derived from hypoxia preconditioned mesenchymal stem cells laden in a silk hydrogel promote cartilage regeneration via the miR-205\u20135p\/PTEN\/AKT pathway. Acta Biomater. 2022;143:173\u201388.","journal-title":"Acta Biomater"},{"key":"4412_CR31","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.actbio.2020.12.034","volume":"122","author":"Y Rong","year":"2021","unstructured":"Rong Y, Zhang J, Jiang D, Ji C, Liu W, Wang J, et al. Hypoxic pretreatment of small extracellular vesicles mediates cartilage repair in osteoarthritis by delivering miR-216a-5p. Acta Biomater. 2021;122:325\u201342.","journal-title":"Acta Biomater"},{"key":"4412_CR32","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/S1877-1173(09)90005-9","volume":"90","author":"CT Pager","year":"2009","unstructured":"Pager CT, Wehner KA, Fuchs G, Sarnow P. MicroRNA-mediated gene Silencing. Prog Mol Biol Transl Sci. 2009;90:187\u2013210.","journal-title":"Prog Mol Biol Transl Sci"},{"key":"4412_CR33","doi-asserted-by":"crossref","unstructured":"Hesse M, Arenz C. MicroRNA maturation and human disease. MiRNA Maturation: Methods Protocols. 2014:11\u201325.","DOI":"10.1007\/978-1-62703-703-7_2"},{"key":"4412_CR34","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.omtn.2019.04.027","volume":"16","author":"M Wang","year":"2019","unstructured":"Wang M, Yu F, Ding H, Wang Y, Li P, Wang K. Emerging function and clinical values of Exosomal MicroRNAs in cancer. Mol therapy-Nucleic Acids. 2019;16:791\u2013804.","journal-title":"Mol therapy-Nucleic Acids"},{"key":"4412_CR35","doi-asserted-by":"publisher","first-page":"111177","DOI":"10.1016\/j.intimp.2023.111177","volume":"125","author":"Y Ji","year":"2023","unstructured":"Ji Y, Xiong L, Zhang G, Xu M, Qiu W, Xiu C, et al. Synovial fluid exosome-derived miR-182-5p alleviates osteoarthritis by downregulating TNFAIP8 and promoting autophagy through LC3 signaling. Int Immunopharmacol. 2023;125:111177.","journal-title":"Int Immunopharmacol"},{"issue":"3","key":"4412_CR36","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.molcel.2017.06.025","volume":"67","author":"JM Luna","year":"2017","unstructured":"Luna JM, Barajas JM, Teng K-y, Sun H-L, Moore MJ, Rice CM, et al. Argonaute CLIP defines a deregulated miR-122-bound transcriptome that correlates with patient survival in human liver cancer. Mol Cell. 2017;67(3):400\u201310. e7.","journal-title":"Mol Cell"},{"key":"4412_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12935-020-01185-z","volume":"20","author":"C Dai","year":"2020","unstructured":"Dai C, Zhang Y, Xu Z, Jin M. MicroRNA-122-5p inhibits cell proliferation, migration and invasion by targeting CCNG1 in pancreatic ductal adenocarcinoma. Cancer Cell Int. 2020;20:1\u201318.","journal-title":"Cancer Cell Int"},{"issue":"2","key":"4412_CR38","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1007\/s11626-022-00651-4","volume":"58","author":"M Yang","year":"2022","unstructured":"Yang M, Song J-J, Yang X-C, Zhong G-Z, Zhong J-C. MiRNA-122-5p inhibitor abolishes angiotensin II\u2013mediated loss of autophagy and promotion of apoptosis in rat cardiofibroblasts by modulation of the apelin-AMPK-mTOR signaling. Vitro Cell Dev Biology-Animal. 2022;58(2):136\u201348.","journal-title":"Vitro Cell Dev Biology-Animal"},{"issue":"6","key":"4412_CR39","first-page":"2852","volume":"9","author":"R Kong","year":"2017","unstructured":"Kong R, Gao J, Si Y, Zhao D. Combination of Circulating miR-19b-3p, miR-122-5p and miR-486-5p expressions correlates with risk and disease severity of knee osteoarthritis. Am J Translational Res. 2017;9(6):2852.","journal-title":"Am J Translational Res"},{"key":"4412_CR40","doi-asserted-by":"crossref","unstructured":"Yadav R, Srivastava RN, Kumar D, Sharma A, Srivastava SR, Pant S et al. Role of serum Micro-RNA-122-5p expression as a circulatory biomarker in people having both knee osteoarthritis and osteoporosis: A Case-Control study. Cureus. 2024;16(5).","DOI":"10.7759\/cureus.60844"},{"issue":"5","key":"4412_CR41","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/nrd2289","volume":"6","author":"KL Jeffrey","year":"2007","unstructured":"Jeffrey KL, Camps M, Rommel C, Mackay CR. Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Discovery. 2007;6(5):391\u2013403.","journal-title":"Nat Rev Drug Discovery"},{"issue":"5102","key":"4412_CR42","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1126\/science.7681221","volume":"259","author":"PJ Rohan","year":"1993","unstructured":"Rohan PJ, Davis P, Moskaluk CA, Kearns M, Krutzsch H, Siebenlist U, et al. PAC-1: a mitogen-induced nuclear protein tyrosine phosphatase. Science. 1993;259(5102):1763\u20136.","journal-title":"Science"},{"issue":"1","key":"4412_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/gene.2012.54","volume":"14","author":"W Wei","year":"2013","unstructured":"Wei W, Jiao Y, Postlethwaite A, Stuart J, Wang Y, Sun D, et al. Dual-specificity phosphatases 2: surprising positive effect at the molecular level and a potential biomarker of diseases. Genes Immun. 2013;14(1):1\u20136.","journal-title":"Genes Immun"},{"issue":"5","key":"4412_CR44","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1172\/JCI44362","volume":"121","author":"S-C Lin","year":"2011","unstructured":"Lin S-C, Chien C-W, Lee J-C, Yeh Y-C, Hsu K-F, Lai Y-Y, et al. Suppression of dual-specificity phosphatase\u20132 by hypoxia increases chemoresistance and malignancy in human cancer cells. J Clin Investig. 2011;121(5):1905\u201316.","journal-title":"J Clin Investig"},{"issue":"6931","key":"4412_CR45","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/nature01519","volume":"422","author":"Y Yin","year":"2003","unstructured":"Yin Y, Liu Y-X, Jin YJ, Hall EJ, Barrett JC. PAC1 phosphatase is a transcription target of p53 in signalling apoptosis and growth suppression. Nature. 2003;422(6931):527\u201331.","journal-title":"Nature"},{"issue":"9","key":"4412_CR46","first-page":"1886","volume":"1843","author":"V Morente","year":"2014","unstructured":"Morente V, P\u00e9rez-Sen R, Ortega F, Huerta-Cepas J, Delicado EG, Miras-Portugal MT. Neuroprotection elicited by P2Y13 receptors against genotoxic stress by inducing DUSP2 expression and MAPK signaling recovery. Biochimica et biophysica acta (BBA)-Molecular. Cell Res. 2014;1843(9):1886\u201398.","journal-title":"Cell Res"},{"key":"4412_CR47","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1007\/s10753-016-0435-y","volume":"39","author":"Z Yao","year":"2016","unstructured":"Yao Z, Nie L, Zhao Y, Zhang Y, Liu Y, Li J, et al. Salubrinal suppresses IL-17-induced upregulation of MMP-13 and extracellular matrix degradation through the NF-kB pathway in human nucleus pulposus cells. Inflammation. 2016;39:1997\u20132007.","journal-title":"Inflammation"},{"issue":"22","key":"4412_CR48","doi-asserted-by":"publisher","first-page":"3203","DOI":"10.1038\/sj.onc.1210412","volume":"26","author":"D Owens","year":"2007","unstructured":"Owens D, Keyse S. Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases. Oncogene. 2007;26(22):3203\u201313.","journal-title":"Oncogene"},{"issue":"11","key":"4412_CR49","doi-asserted-by":"publisher","first-page":"6497","DOI":"10.1074\/jbc.271.11.6497","volume":"271","author":"Y Chu","year":"1996","unstructured":"Chu Y, Solski PA, Khosravi-Far R, Der CJ, Kelly K. The Mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 Sevenmaker mutation (\u2217). J Biol Chem. 1996;271(11):6497\u2013501.","journal-title":"J Biol Chem"},{"issue":"6464","key":"4412_CR50","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/367651a0","volume":"367","author":"Y Ward","year":"1994","unstructured":"Ward Y, Gupta S, Jensen P, Wartmann M, Davis RJ, Kelly K. Control of MAP kinase activation by the mitogen-induced threonine\/tyrosine phosphatase PAC1. Nature. 1994;367(6464):651\u20134.","journal-title":"Nature"},{"key":"4412_CR51","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.bioactmat.2022.08.007","volume":"21","author":"T Ye","year":"2023","unstructured":"Ye T, Chen Z, Zhang J, Luo L, Gao R, Gong L, et al. Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tendinopathy via regulating macrophage heterogeneity. Bioactive Mater. 2023;21:194\u2013208.","journal-title":"Bioactive Mater"},{"issue":"8","key":"4412_CR52","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/s41419-018-0839-8","volume":"9","author":"J Hu","year":"2018","unstructured":"Hu J, Li L, Chen H, Zhang G, Liu H, Kong R, et al. MiR-361-3p regulates ERK1\/2-induced EMT via DUSP2 mRNA degradation in pancreatic ductal adenocarcinoma. Cell Death Dis. 2018;9(8):807.","journal-title":"Cell Death Dis"}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04412-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-025-04412-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04412-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T18:02:45Z","timestamp":1749319365000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-025-04412-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,7]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4412"],"URL":"https:\/\/doi.org\/10.1186\/s13287-025-04412-4","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,7]]},"assertion":[{"value":"26 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal procedures were performed according to the guidelines of the Institutional Animal Care and Use Committee at National University of Singapore. Project Title: Cartilage tissue engineering with mesenchymal stem cells and extracellular vesicles from manipulated MSCs. Protocol number: R2020-0258. Approval date: 21\/05\/2020.The access to human OA cartilage tissues was according to the guidelines of National Healthcare Group Domain Specific Review Board (NHG DSRB Ref: 2024\u20133392). Study title: Zonal chondrocytes for improved strategy of autologous chondrocyte implantation in cartilage repair. Approval date: 09\/10\/2024.The original source for hMSC (Lonza; as stated in their Certificate of Analysis) and 293T\/17 (ATCC, file:\/\/\/C:\/Users\/dosyz\/Downloads\/CRL-11268%20Product%20Sheet%20-%20293T_17%20[HEK%20293T_17]%20 []. pdf) have confirmed that there was initial approval for collection of these human cell, and that the donors had signed informed consent. The information can be found on company website.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent to participate in research study has been obtained.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors report no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"289"}}