{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:53:20Z","timestamp":1793332400814,"version":"4.5.0"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Yunnan Provincial Department of Education Project","award":["2024Y253"],"award-info":[{"award-number":["2024Y253"]}],"id":[{"id":"https:\/\/ror.org\/02yrxdp92","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970515"],"award-info":[{"award-number":["31970515"]}],"id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yunnan Provincial Plan Project","award":["202301AY070001-022"],"award-info":[{"award-number":["202301AY070001-022"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton\u2019s jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-\u03b2\/Smad2\/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50\u00a0\u00b5g\/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-\u03b2, and Smad2\/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s12951-024-02451-2","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T12:02:16Z","timestamp":1712923336000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1\/TGF-\u03b2\/Smad2\/3 axis mediated by microfractures"],"prefix":"10.1186","volume":"22","author":[{"given":"Zhian","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongmao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongqing","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"issue":"6","key":"2451_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. https:\/\/doi.org\/10.1001\/jama.2020.22171.","journal-title":"JAMA"},{"issue":"4","key":"2451_CR2","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s00264-009-0940-9","volume":"35","author":"T Floerkemeier","year":"2011","unstructured":"Floerkemeier T, Thorey F, Daentzer D, Lerch M, Klages P, Windhagen H, von Lewinski G. Clinical and radiological outcome of the treatment of osteonecrosis of the femoral head using the osteonecrosis intervention implant. Int Orthop. 2011;35(4):489\u201395. https:\/\/doi.org\/10.1007\/s00264-009-0940-9.","journal-title":"Int Orthop"},{"key":"2451_CR3","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jot.2019.12.004","volume":"21","author":"D Zhao","year":"2020","unstructured":"Zhao D, Zhang F, Wang B, Liu B, Li L, Kim SY, et al. Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version). J Orthop Translat. 2020;21:100\u201310. https:\/\/doi.org\/10.1016\/j.jot.2019.12.004.","journal-title":"J Orthop Translat."},{"issue":"609","key":"2451_CR4","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz4499","volume":"13","author":"L Acevedo Rua","year":"2021","unstructured":"Acevedo Rua L, Mumme M, Manferdini C, Darwiche S, Khalil A, Hilpert M, et al. Engineered nasal cartilage for the repair of osteoarthritic knee cartilage defects. Sci Transl Med. 2021;13(609): eaaz4499. https:\/\/doi.org\/10.1126\/scitranslmed.aaz4499.","journal-title":"Sci Transl Med."},{"issue":"24","key":"2451_CR5","doi-asserted-by":"publisher","first-page":"25138","DOI":"10.18632\/aging.104110","volume":"12","author":"J Zhang","year":"2020","unstructured":"Zhang J, Rong Y, Luo C, Cui W. Bone marrow mesenchymal stem cell-derived exosomes prevent osteoarthritis by regulating synovial macrophage polarization. Aging. 2020;12(24):25138\u201352. https:\/\/doi.org\/10.18632\/aging.104110.","journal-title":"Aging"},{"issue":"9","key":"2451_CR6","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1177\/03635465211008655","volume":"49","author":"CA Logan","year":"2021","unstructured":"Logan CA, Gao X, Utsunomiya H, Scibetta AC, Talwar M, Ravuri SK, et al. The beneficial effect of an intra-articular injection of Losartan on microfracture-mediated cartilage repair is dose dependent. Am J Sports Med. 2021;49(9):2509\u201321. https:\/\/doi.org\/10.1177\/03635465211008655.","journal-title":"Am J Sports Med"},{"issue":"10","key":"2451_CR7","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1177\/0363546508328414","volume":"37","author":"K Mithoefer","year":"2009","unstructured":"Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med. 2009;37(10):2053\u201363. https:\/\/doi.org\/10.1177\/0363546508328414.","journal-title":"Am J Sports Med"},{"issue":"10","key":"2451_CR8","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1038\/s41591-020-1013-2","volume":"26","author":"MP Murphy","year":"2020","unstructured":"Murphy MP, Koepke LS, Lopez MT, Tong X, Ambrosi TH, Gulati GS, et al. Articular cartilage regeneration by activated skeletal stem cells. Nat Med. 2020;26(10):1583\u201392. https:\/\/doi.org\/10.1038\/s41591-020-1013-2.","journal-title":"Nat Med"},{"issue":"8","key":"2451_CR9","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/s41551-021-00696-y","volume":"5","author":"J Fang","year":"2021","unstructured":"Fang J, Sia J, Soto J, Wang P, Li LK, Hsueh YY, et al. Skeletal muscle regeneration via the chemical induction and expansion of myogenic stem cells in situ or in vitro. Nat Biomed Eng. 2021;5(8):864\u201379. https:\/\/doi.org\/10.1038\/s41551-021-00696-y.","journal-title":"Nat Biomed Eng."},{"issue":"5","key":"2451_CR10","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/s41580-022-00568-6","volume":"24","author":"A de Morree","year":"2023","unstructured":"de Morree A, Rando TA. Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity. Nat Rev Mol Cell Biol. 2023;24(5):334\u201354. https:\/\/doi.org\/10.1038\/s41580-022-00568-6.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2451_CR11","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977","author":"R Kalluri","year":"2020","unstructured":"Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020. https:\/\/doi.org\/10.1126\/science.aau6977.","journal-title":"Science"},{"issue":"15","key":"2451_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202103222","volume":"9","author":"JJ Lai","year":"2022","unstructured":"Lai JJ, Chau ZL, Chen SY, Hill JJ, Korpany KV, Liang NW, et al. Exosome processing and characterization approaches for research and technology development. Adv Sci. 2022;9(15): e2103222. https:\/\/doi.org\/10.1002\/advs.202103222.","journal-title":"Adv Sci"},{"issue":"8","key":"2451_CR13","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.7150\/thno.41580","volume":"10","author":"D Yang","year":"2020","unstructured":"Yang D, Zhang W, Zhang H, Zhang F, Chen L, Ma L, et al. Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics. Theranostics. 2020;10(8):3684\u2013707. https:\/\/doi.org\/10.7150\/thno.41580.","journal-title":"Theranostics"},{"issue":"9","key":"2451_CR14","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1016\/j.bioactmat.2021.01.031","volume":"6","author":"S Jiang","year":"2021","unstructured":"Jiang S, Tian G, Yang Z, Gao X, Wang F, Li J, et al. Enhancement of acellular cartilage matrix scaffold by Wharton\u2019s jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration. Bioact Mater. 2021;6(9):2711\u201328. https:\/\/doi.org\/10.1016\/j.bioactmat.2021.01.031.","journal-title":"Bioact Mater."},{"issue":"8","key":"2451_CR15","doi-asserted-by":"publisher","first-page":"13143","DOI":"10.1021\/acsomega.9b01180","volume":"4","author":"N Chopra","year":"2019","unstructured":"Chopra N, Dutt Arya B, Jain N, Yadav P, Wajid S, Singh SP, Choudhury S. Biophysical characterization and drug delivery potential of exosomes from Human Wharton\u2019s Jelly-derived mesenchymal stem cells. ACS Omega. 2019;4(8):13143\u201352. https:\/\/doi.org\/10.1021\/acsomega.9b01180.","journal-title":"ACS Omega"},{"key":"2451_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2023.110604","volume":"105","author":"Z Chen","year":"2023","unstructured":"Chen Z, Ding W, Duan P, Lv X, Feng Y, Yin Z, et al. HWJMSC-derived extracellular vesicles ameliorate IL-1\u03b2-induced chondrocyte injury through regulation of the BMP2\/RUNX2 axis via up-regulation TFRC. Cell Signal. 2023;105: 110604. https:\/\/doi.org\/10.1016\/j.cellsig.2023.110604.","journal-title":"Cell Signal"},{"issue":"11","key":"2451_CR17","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12137","volume":"10","author":"M Nakazaki","year":"2021","unstructured":"Nakazaki M, Morita T, Lankford KL, Askenase PW, Kocsis JD. Small extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF-\u03b2 upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury. J Extracell Vesicles. 2021;10(11): e12137. https:\/\/doi.org\/10.1002\/jev2.12137.","journal-title":"J Extracell Vesicles."},{"issue":"1","key":"2451_CR18","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41392-023-01477-6","volume":"8","author":"X Hu","year":"2023","unstructured":"Hu X, Xu W, Ren Y, Wang Z, He X, Huang R, et al. Spinal cord injury: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2023;8(1):245. https:\/\/doi.org\/10.1038\/s41392-023-01477-6.","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"2451_CR19","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1186\/s13287-020-01792-7","volume":"11","author":"Y Wang","year":"2020","unstructured":"Wang Y, Guo YF, Fu GP, Guan C, Zhang X, Yang DG, Shi YC. Protective effect of miRNA-containing extracellular vesicles derived from mesenchymal stromal cells of old rats on renal function in chronic kidney disease. Stem Cell Res Ther. 2020;11(1):274. https:\/\/doi.org\/10.1186\/s13287-020-01792-7.","journal-title":"Stem Cell Res Ther"},{"issue":"2","key":"2451_CR20","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1172\/jci70050","volume":"124","author":"JL Crane","year":"2014","unstructured":"Crane JL, Cao X. Bone marrow mesenchymal stem cells and TGF-\u03b2 signaling in bone remodeling. J Clin Invest. 2014;124(2):466\u201372. https:\/\/doi.org\/10.1172\/jci70050.","journal-title":"J Clin Invest"},{"issue":"7","key":"2451_CR21","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1038\/nm.1979","volume":"15","author":"Y Tang","year":"2009","unstructured":"Tang Y, Wu X, Lei W, Pang L, Wan C, Shi Z, et al. TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med. 2009;15(7):757\u201365. https:\/\/doi.org\/10.1038\/nm.1979.","journal-title":"Nat Med"},{"issue":"1","key":"2451_CR22","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1186\/s13287-018-0921-2","volume":"9","author":"N Bakhtyar","year":"2018","unstructured":"Bakhtyar N, Jeschke MG, Herer E, Sheikholeslam M, Amini-Nik S. Exosomes from acellular Wharton\u2019s jelly of the human umbilical cord promotes skin wound healing. Stem Cell Res Ther. 2018;9(1):193. https:\/\/doi.org\/10.1186\/s13287-018-0921-2.","journal-title":"Stem Cell Res Ther"},{"issue":"6","key":"2451_CR23","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s10735-020-09918-0","volume":"51","author":"S Luo","year":"2020","unstructured":"Luo S, Shi Q, Li W, Wu W, Zha Z. ITGB1 promotes the chondrogenic differentiation of human adipose-derived mesenchymal stem cells by activating the ERK signaling. J Mol Histol. 2020;51(6):729\u201339. https:\/\/doi.org\/10.1007\/s10735-020-09918-0.","journal-title":"J Mol Histol"},{"key":"2451_CR24","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/s41413-019-0046-y","volume":"7","author":"C Lian","year":"2019","unstructured":"Lian C, Wang X, Qiu X, Wu Z, Gao B, Liu L, et al. Collagen type II suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin \u03b21-SMAD1 interaction. Bone Res. 2019;7:8. https:\/\/doi.org\/10.1038\/s41413-019-0046-y.","journal-title":"Bone Res."},{"issue":"8","key":"2451_CR25","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1002\/jcp.22530","volume":"226","author":"LH Chiu","year":"2011","unstructured":"Chiu LH, Chen SC, Wu KC, Yang CB, Fang CL, Lai WF, Tsai YH. Differential effect of ECM molecules on re-expression of cartilaginous markers in near quiescent human chondrocytes. J Cell Physiol. 2011;226(8):1981\u20138. https:\/\/doi.org\/10.1002\/jcp.22530.","journal-title":"J Cell Physiol"},{"issue":"7835","key":"2451_CR26","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41586-020-2938-9","volume":"587","author":"NC Henderson","year":"2020","unstructured":"Henderson NC, Rieder F, Wynn TA. Fibrosis: from mechanisms to medicines. Nature. 2020;587(7835):555\u201366. https:\/\/doi.org\/10.1038\/s41586-020-2938-9.","journal-title":"Nature"},{"issue":"3","key":"2451_CR27","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1002\/jbmr.3902","volume":"35","author":"M Liu","year":"2020","unstructured":"Liu M, Alharbi M, Graves D, Yang S. IFT80 Is required for fracture healing through controlling the regulation of TGF-\u03b2 signaling in chondrocyte differentiation and function. J Bone Miner Res. 2020;35(3):571\u201382. https:\/\/doi.org\/10.1002\/jbmr.3902.","journal-title":"J Bone Miner Res"},{"key":"2451_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102373","volume":"54","author":"Y Li","year":"2022","unstructured":"Li Y, Yang S, Liu Y, Qin L, Yang S. IFT20 governs mesenchymal stem cell fate through positively regulating TGF-\u03b2-Smad2\/3-Glut1 signaling mediated glucose metabolism. Redox Biol. 2022;54: 102373. https:\/\/doi.org\/10.1016\/j.redox.2022.102373.","journal-title":"Redox Biol"},{"key":"2451_CR29","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.900205","volume":"14","author":"Y Ge","year":"2023","unstructured":"Ge Y, Xu W, Chen Z, Zhang H, Zhang W, Chen J, et al. Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-\u03b2-Smad2\/3 signaling of chondrocytes. Front Pharmacol. 2023;14: 900205. https:\/\/doi.org\/10.3389\/fphar.2023.900205.","journal-title":"Front Pharmacol"},{"issue":"8","key":"2451_CR30","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1136\/annrheumdis-2019-216911","volume":"79","author":"G Wang","year":"2020","unstructured":"Wang G, Chen S, Xie Z, Shen S, Xu W, Chen W, et al. TGF\u03b2 attenuates cartilage extracellular matrix degradation via enhancing FBXO6-mediated MMP14 ubiquitination. Ann Rheum Dis. 2020;79(8):1111\u201320. https:\/\/doi.org\/10.1136\/annrheumdis-2019-216911.","journal-title":"Ann Rheum Dis"},{"issue":"11","key":"2451_CR31","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1038\/s41419-021-04363-7","volume":"12","author":"L Zhang","year":"2021","unstructured":"Zhang L, Wei W, Ai X, Kilic E, Hermann DM, Venkataramani V, B\u00e4hr M, Doeppner TR. Extracellular vesicles from hypoxia-preconditioned microglia promote angiogenesis and repress apoptosis in stroke mice via the TGF-\u03b2\/Smad2\/3 pathway. Cell Death Dis. 2021;12(11):1068. https:\/\/doi.org\/10.1038\/s41419-021-04363-7.","journal-title":"Cell Death Dis"},{"issue":"1","key":"2451_CR32","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s12943-019-1101-4","volume":"18","author":"J Kong","year":"2019","unstructured":"Kong J, Tian H, Zhang F, Zhang Z, Li J, Liu X, et al. Extracellular vesicles of carcinoma-associated fibroblasts creates a pre-metastatic niche in the lung through activating fibroblasts. Mol Cancer. 2019;18(1):175. https:\/\/doi.org\/10.1186\/s12943-019-1101-4.","journal-title":"Mol Cancer"},{"key":"2451_CR33","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.bioactmat.2022.01.016","volume":"17","author":"Z Luo","year":"2022","unstructured":"Luo Z, Sun Y, Qi B, Lin J, Chen Y, Xu Y, Chen J. Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a\/Tgfbr1 axis. Bioact Mater. 2022;17:344\u201359. https:\/\/doi.org\/10.1016\/j.bioactmat.2022.01.016.","journal-title":"Bioact Mater."},{"issue":"7","key":"2451_CR34","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1177\/03635465211005102","volume":"49","author":"H Utsunomiya","year":"2021","unstructured":"Utsunomiya H, Gao X, Cheng H, Deng Z, Nakama G, Mascarenhas R, et al. Intra-articular injection of bevacizumab enhances bone marrow stimulation-mediated cartilage repair in a rabbit osteochondral defect model. Am J Sports Med. 2021;49(7):1871\u201382. https:\/\/doi.org\/10.1177\/03635465211005102.","journal-title":"Am J Sports Med"},{"issue":"1","key":"2451_CR35","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.actbio.2009.07.041","volume":"6","author":"X Guo","year":"2010","unstructured":"Guo X, Park H, Young S, Kretlow JD, van den Beucken JJ, Baggett LS, et al. Repair of osteochondral defects with biodegradable hydrogel composites encapsulating marrow mesenchymal stem cells in a rabbit model. Acta Biomater. 2010;6(1):39\u201347. https:\/\/doi.org\/10.1016\/j.actbio.2009.07.041.","journal-title":"Acta Biomater"},{"key":"2451_CR36","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192080","author":"KM Mahuron","year":"2020","unstructured":"Mahuron KM, Moreau JM, Glasgow JE, Boda DP, Pauli ML, Gouirand V, et al. Layilin augments integrin activation to promote antitumor immunity. J Exp Med. 2020. https:\/\/doi.org\/10.1084\/jem.20192080.","journal-title":"J Exp Med"},{"key":"2451_CR37","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122037","author":"D Bianconi","year":"2016","unstructured":"Bianconi D, Unseld M, Prager GW. Integrins in the spotlight of cancer. Int J Mol Sci. 2016. https:\/\/doi.org\/10.3390\/ijms17122037.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2451_CR38","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/0092-8674(92)90115-s","volume":"69","author":"RO Hynes","year":"1992","unstructured":"Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992;69(1):11\u201325. https:\/\/doi.org\/10.1016\/0092-8674(92)90115-s.","journal-title":"Cell"},{"issue":"8","key":"2451_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107200","volume":"26","author":"Z Deng","year":"2023","unstructured":"Deng Z, Rong S, Gan L, Wang F, Bao L, Cai F, et al. Temporal transcriptome features identify early skeletal commitment during human epiphysis development at single-cell resolution. iScience. 2023;26(8): 107200. https:\/\/doi.org\/10.1016\/j.isci.2023.107200.","journal-title":"iScience."},{"issue":"6","key":"2451_CR40","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1002\/jcsm.12767","volume":"12","author":"W Luo","year":"2021","unstructured":"Luo W, Lin Z, Chen J, Chen G, Zhang S, Liu M, et al. TMEM182 interacts with integrin beta 1 and regulates myoblast differentiation and muscle regeneration. J Cachexia Sarcopenia Muscle. 2021;12(6):1704\u201323. https:\/\/doi.org\/10.1002\/jcsm.12767.","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"24","key":"2451_CR41","doi-asserted-by":"publisher","first-page":"3980","DOI":"10.1111\/jcmm.17976","volume":"27","author":"R Qi","year":"2023","unstructured":"Qi R, Hou J, Yang Y, Yang Z, Wu L, Qiao T, Wang X, Song D. Integrin beta1 mediates the effect of telocytes on mesenchymal stem cell proliferation and migration in the treatment of acute lung injury. J Cell Mol Med. 2023;27(24):3980\u201394. https:\/\/doi.org\/10.1111\/jcmm.17976.","journal-title":"J Cell Mol Med"},{"key":"2451_CR42","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115428","author":"I Zhivodernikov","year":"2021","unstructured":"Zhivodernikov I, Ratushnyy A, Buravkova L. Simulated microgravity remodels extracellular matrix of osteocommitted mesenchymal stromal cells. Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms22115428.","journal-title":"Int J Mol Sci"},{"issue":"5","key":"2451_CR43","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/s12276-022-00778-0","volume":"54","author":"Z Zhao","year":"2022","unstructured":"Zhao Z, Zhang Y, Zhang C, Zhang J, Luo X, Qiu Q, Luo D, Zhang J. TGF-\u03b2 promotes pericyte-myofibroblast transition in subretinal fibrosis through the Smad2\/3 and Akt\/mTOR pathways. Exp Mol Med. 2022;54(5):673\u201384. https:\/\/doi.org\/10.1038\/s12276-022-00778-0.","journal-title":"Exp Mol Med"},{"issue":"10","key":"2451_CR44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006352","volume":"12","author":"W Wang","year":"2016","unstructured":"Wang W, Song B, Anbarchian T, Shirazyan A, Sadik JE, Lyons KM. Smad2 and Smad3 regulate chondrocyte proliferation and differentiation in the growth plate. PLoS Genet. 2016;12(10): e1006352. https:\/\/doi.org\/10.1371\/journal.pgen.1006352.","journal-title":"PLoS Genet"},{"issue":"1","key":"2451_CR45","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13287-020-1552-y","volume":"11","author":"SN Li","year":"2020","unstructured":"Li SN, Wu JF. TGF-\u03b2\/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment. Stem Cell Res Ther. 2020;11(1):41. https:\/\/doi.org\/10.1186\/s13287-020-1552-y.","journal-title":"Stem Cell Res Ther"},{"key":"2451_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114216","volume":"159","author":"Y Wang","year":"2023","unstructured":"Wang Y, Jin Z, Jia S, Shen P, Yang Y, Huang Y. Mechanical stress protects against chondrocyte pyroptosis through TGF-\u03b21-mediated activation of Smad2\/3 and inhibition of the NF-\u03baB signaling pathway in an osteoarthritis model. Biomed Pharmacother. 2023;159: 114216. https:\/\/doi.org\/10.1016\/j.biopha.2023.114216.","journal-title":"Biomed Pharmacother"},{"key":"2451_CR47","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.lfs.2017.11.028","volume":"192","author":"J Ying","year":"2018","unstructured":"Ying J, Wang P, Zhang S, Xu T, Zhang L, Dong R, et al. Transforming growth factor-beta1 promotes articular cartilage repair through canonical Smad and Hippo pathways in bone mesenchymal stem cells. Life Sci. 2018;192:84\u201390. https:\/\/doi.org\/10.1016\/j.lfs.2017.11.028.","journal-title":"Life Sci"},{"issue":"13","key":"2451_CR48","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1042\/cs20220082","volume":"136","author":"X Ma","year":"2022","unstructured":"Ma X, Cai D, Zhu Y, Zhao Y, Shang X, Wang C, et al. L-Glutamine alleviates osteoarthritis by regulating lncRNA-NKILA expression through the TGF-\u03b21\/SMAD2\/3 signalling pathway. Clin Sci. 2022;136(13):1053\u201369. https:\/\/doi.org\/10.1042\/cs20220082.","journal-title":"Clin Sci"},{"key":"2451_CR49","doi-asserted-by":"publisher","first-page":"3177","DOI":"10.2147\/ijn.S407029","volume":"18","author":"YG Yuan","year":"2023","unstructured":"Yuan YG, Wang JL, Zhang YX, Li L, Reza A, Gurunathan S. Biogenesis, composition and potential therapeutic applications of mesenchymal stem cells derived exosomes in various diseases. Int J Nanomed. 2023;18:3177\u2013210. https:\/\/doi.org\/10.2147\/ijn.S407029.","journal-title":"Int J Nanomed"},{"key":"2451_CR50","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22189701","author":"T Spakova","year":"2021","unstructured":"Spakova T, Janockova J, Rosocha J. Characterization and therapeutic use of extracellular vesicles derived from platelets. Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms22189701.","journal-title":"Int J Mol Sci"},{"key":"2451_CR51","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 WN, 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. https:\/\/doi.org\/10.1016\/j.biomaterials.2019.03.022.","journal-title":"Biomaterials"},{"issue":"1","key":"2451_CR52","doi-asserted-by":"publisher","first-page":"180","DOI":"10.7150\/thno.17133","volume":"7","author":"SC Tao","year":"2017","unstructured":"Tao SC, Yuan T, Zhang YL, Yin WJ, Guo SC, Zhang CQ. 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. Theranostics. 2017;7(1):180\u201395. https:\/\/doi.org\/10.7150\/thno.17133.","journal-title":"Theranostics"},{"issue":"4","key":"2451_CR53","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1177\/03635465221073991","volume":"50","author":"Y Liu","year":"2022","unstructured":"Liu Y, Zeng Y, Si HB, Tang L, Xie HQ, Shen B. Exosomes derived from human urine-derived stem cells overexpressing miR-140\u20135p alleviate knee osteoarthritis through downregulation of VEGFA in a rat model. Am J Sports Med. 2022;50(4):1088\u2013105. https:\/\/doi.org\/10.1177\/03635465221073991.","journal-title":"Am J Sports Med"},{"issue":"4","key":"2451_CR54","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/stem.3322","volume":"39","author":"L Luo","year":"2021","unstructured":"Luo L, Jian X, Sun H, Qin J, Wang Y, Zhang J, et al. Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt\/autophagy. Stem Cells. 2021;39(4):467\u201381. https:\/\/doi.org\/10.1002\/stem.3322.","journal-title":"Stem Cells"},{"issue":"11","key":"2451_CR55","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1177\/03635465231188122","volume":"51","author":"C Xu","year":"2023","unstructured":"Xu C, Mi Z, Dong Z, Chen X, Ji G, Kang H, Li K, Zhao B, Wang F. Platelet-derived exosomes alleviate knee osteoarthritis by attenuating cartilage degeneration and subchondral bone loss. Am J Sports Med. 2023;51(11):2975\u201385. https:\/\/doi.org\/10.1177\/03635465231188122.","journal-title":"Am J Sports Med"},{"issue":"1","key":"2451_CR56","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/s41420-022-00971-0","volume":"8","author":"S Fang","year":"2022","unstructured":"Fang S, Liu Z, Wu S, Chen X, You M, Li Y, et al. Pro-angiognetic and pro-osteogenic effects of human umbilical cord mesenchymal stem cell-derived exosomal miR-21-5p in osteonecrosis of the femoral head. Cell Death Discov. 2022;8(1):226. https:\/\/doi.org\/10.1038\/s41420-022-00971-0.","journal-title":"Cell Death Discov"},{"issue":"4","key":"2451_CR57","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202204786","volume":"10","author":"P Chen","year":"2023","unstructured":"Chen P, Tang S, Li M, Wang D, Chen C, Qiu Y, et al. Single-cell and spatial transcriptomics decodes Wharton\u2019s Jelly-derived mesenchymal stem cells heterogeneity and a subpopulation with wound repair signatures. Adv Sci. 2023;10(4): e2204786. https:\/\/doi.org\/10.1002\/advs.202204786.","journal-title":"Adv Sci"},{"issue":"1","key":"2451_CR58","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s11658-023-00485-2","volume":"28","author":"Z Zhang","year":"2023","unstructured":"Zhang Z, Zhao S, Sun Z, Zhai C, Xia J, Wen C, Zhang Y, Zhang Y. Enhancement of the therapeutic efficacy of mesenchymal stem cell-derived exosomes in osteoarthritis. Cell Mol Biol Lett. 2023;28(1):75. https:\/\/doi.org\/10.1186\/s11658-023-00485-2.","journal-title":"Cell Mol Biol Lett"},{"key":"2451_CR59","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.actbio.2020.07.008","volume":"114","author":"Z Yang","year":"2020","unstructured":"Yang Z, Li H, Yuan Z, Fu L, Jiang S, Gao C, et al. Endogenous cell recruitment strategy for articular cartilage regeneration. Acta Biomater. 2020;114:31\u201352. https:\/\/doi.org\/10.1016\/j.actbio.2020.07.008.","journal-title":"Acta Biomater"},{"issue":"8","key":"2451_CR60","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101156","volume":"4","author":"J Wei","year":"2023","unstructured":"Wei J, Baptista-Hon DT, Wang Z, Li G, Herrler T, Dai C, et al. Bioengineered human tissue regeneration and repair using endogenous stem cells. Cell Rep Med. 2023;4(8): 101156. https:\/\/doi.org\/10.1016\/j.xcrm.2023.101156.","journal-title":"Cell Rep Med"},{"issue":"3","key":"2451_CR61","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1177\/03635465211003595","volume":"50","author":"T Abraamyan","year":"2022","unstructured":"Abraamyan T, Johnson AJ, Wiedrick J, Crawford DC. Marrow stimulation has relatively inferior patient-reported outcomes in cartilage restoration surgery of the knee: a systematic review and meta-analysis of randomized controlled trials. Am J Sports Med. 2022;50(3):858\u201366. https:\/\/doi.org\/10.1177\/03635465211003595.","journal-title":"Am J Sports Med"},{"issue":"4","key":"2451_CR62","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1177\/0363546517701912","volume":"46","author":"MJ Kraeutler","year":"2018","unstructured":"Kraeutler MJ, Belk JW, Purcell JM, McCarty EC. Microfracture versus autologous chondrocyte implantation for articular cartilage lesions in the knee: a systematic review of 5-year outcomes. Am J Sports Med. 2018;46(4):995\u20139. https:\/\/doi.org\/10.1177\/0363546517701912.","journal-title":"Am J Sports Med"},{"issue":"1","key":"2451_CR63","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202201588","volume":"12","author":"Z Mao","year":"2023","unstructured":"Mao Z, Bi X, Wu C, Zheng Y, Shu X, Wu S, Guan J, Ritchie RO. A cell-free silk fibroin biomaterial strategy promotes in situ cartilage regeneration via programmed releases of bioactive molecules. Adv Healthc Mater. 2023;12(1): e2201588. https:\/\/doi.org\/10.1002\/adhm.202201588.","journal-title":"Adv Healthc Mater."},{"issue":"1","key":"2451_CR64","doi-asserted-by":"publisher","first-page":"1914","DOI":"10.1038\/s41467-019-09839-x","volume":"10","author":"Y Shi","year":"2019","unstructured":"Shi Y, Hu X, Cheng J, Zhang X, Zhao F, Shi W, et al. A small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development. Nat Commun. 2019;10(1):1914. https:\/\/doi.org\/10.1038\/s41467-019-09839-x.","journal-title":"Nat Commun"},{"key":"2451_CR65","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12967-015-0417-0","volume":"13","author":"J Zhang","year":"2015","unstructured":"Zhang J, Guan J, Niu X, Hu G, Guo S, Li Q, Xie Z, Zhang C, Wang Y. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J Transl Med. 2015;13:49. https:\/\/doi.org\/10.1186\/s12967-015-0417-0.","journal-title":"J Transl Med"},{"issue":"40","key":"2451_CR66","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202101558","volume":"33","author":"HS Kim","year":"2021","unstructured":"Kim HS, Shin YM, Chung S, Kim D, Park DB, Baek S, et al. Cell-membrane-derived nanoparticles with notch-1 suppressor delivery promote hypoxic cell-cell packing and inhibit angiogenesis acting as a two-edged sword. Adv Mater. 2021;33(40): e2101558. https:\/\/doi.org\/10.1002\/adma.202101558.","journal-title":"Adv Mater"},{"key":"2451_CR67","doi-asserted-by":"publisher","DOI":"10.3390\/cells8030258","author":"DN Silachev","year":"2019","unstructured":"Silachev DN, Goryunov KV, Shpilyuk MA, Beznoschenko OS, Morozova NY, Kraevaya EE, et al. Effect of MSCs and MSC-derived extracellular vesicles on human blood coagulation. Cells. 2019. https:\/\/doi.org\/10.3390\/cells8030258.","journal-title":"Cells"}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-024-02451-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12951-024-02451-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-024-02451-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T12:05:31Z","timestamp":1712923531000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-024-02451-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,12]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2451"],"URL":"https:\/\/doi.org\/10.1186\/s12951-024-02451-2","relation":{},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,12]]},"assertion":[{"value":"8 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animal studies were approved by the Ethics Committee of the 920th Hospital of the Joint Logistics Support Force.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors read and agreed to submit the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"177"}}