{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T10:48:21Z","timestamp":1782730101205,"version":"3.54.5"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82575115"],"award-info":[{"award-number":["82575115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Adipose-derived mesenchymal stem cell (ADMSC) exosomes have emerged as promising therapeutic agents for degenerative joint diseases, yet their molecular actions in knee osteoarthritis (KOA) remain inadequately defined. In this study, exosomes were isolated from ADMSCs under both physiological and IL-1\u03b2-induced inflammatory conditions and comprehensively characterized by NTA, TEM, and exosome marker expression. Both types of exosomes were efficiently internalized by chondrocytes, with uptake reaching saturation after 12\u2009hours regardless of inflammatory status. Functional assays revealed that while exosomes from healthy ADMSCs (EXOs) significantly enhanced levels of mitochondrial fusion proteins and decreased fission marker in IL-1\u03b2-induced chondrocytes after 24\u2009hours, these beneficial effects were absent in exosomes derived from inflamed ADMSCs (IL-1\u03b2 EXOs). Notably, EXO treatment reduced intracellular ROS accumulation, boosted SOD2 levels, and diminished apoptotic cell rates in chondrocytes. In vivo, administration of EXOs to rats with ACLT-induced KOA markedly alleviated cartilage degeneration, restoration of mitochondrial dynamics, and suppression of inflammatory and matrix-degrading mediators. Transcriptomic analysis showed that EXOs activated gene expression programs related to fatty acid metabolism, oxidative phosphorylation, and AMPK signaling, while IL-1\u03b2 EXOs enriched inflammatory and apoptotic pathways. Importantly, both genetic knockdown and pharmacological inhibition of AMPK abolished the restorative effects of EXOs on mitochondrial dynamics and on the reduction of apoptotic markers both ex vivo and in vivo. These findings demonstrate that exosomes secreted by ADMSCs preserve cartilage integrity in KOA via AMPK-mediated mitochondrial dynamics. This work supports AMPK-targeted modulation of mitochondrial dynamics by stem cell exosomes as a promising disease-modifying strategy for KOA.<\/jats:p>","DOI":"10.1093\/stmcls\/sxag021","type":"journal-article","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T11:38:51Z","timestamp":1776598731000},"source":"Crossref","is-referenced-by-count":0,"title":["Exosomes secreted by ADMSCs preserve cartilage integrity in knee osteoarthritis via AMPK-mediated mitochondrial dynamics and apoptosis"],"prefix":"10.1093","volume":"44","author":[{"given":"Jinliang","family":"He","sequence":"first","affiliation":[{"name":"Shanxi University of Chinese Medicine , Taiyuan, Shanxi 030024,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanxi University of Chinese Medicine , Taiyuan, Shanxi 030024,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Shanxi University of Chinese Medicine , Taiyuan, Shanxi 030024,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Nan","sequence":"additional","affiliation":[{"name":"Shanxi University of Chinese Medicine , Taiyuan, Shanxi 030024,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Te","family":"Ba","sequence":"additional","affiliation":[{"name":"Shanxi University of Chinese Medicine , Taiyuan, Shanxi 030024,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Gao","sequence":"additional","affiliation":[{"name":"Shanxi University of Chinese Medicine , Taiyuan, Shanxi 030024,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9486-4752","authenticated-orcid":false,"given":"Junfeng","family":"Kang","sequence":"additional","affiliation":[{"name":"Shanxi University of Chinese Medicine , Taiyuan, Shanxi 030024,","place":["China"]},{"name":"The Affiliated Hospital of Shanxi University of Chinese Medicine , Taiyuan, Shanxi 030024,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqin","family":"Hao","sequence":"additional","affiliation":[{"name":"Shanxi University of Chinese Medicine , Taiyuan, Shanxi 030024,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"2026062906164749300_sxag021-B1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41572-025-00594-6","article-title":"Osteoarthritis","volume":"11","author":"Tang","year":"2025","journal-title":"Nat Rev Dis Primers"},{"key":"2026062906164749300_sxag021-B2","doi-asserted-by":"crossref","first-page":"e508","DOI":"10.1016\/S2665-9913(23)00163-7","article-title":"Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: a systematic analysis for the global burden of disease study 2021","volume":"5","author":"GBD 2021 Osteoarthritis Collaborators","year":"2023","journal-title":"Lancet Rheumatol"},{"key":"2026062906164749300_sxag021-B3","doi-asserted-by":"publisher","first-page":"2501880","DOI":"10.1080\/21655979.2025.2501880","article-title":"Molecular signaling pathways in osteoarthritis and biomaterials for cartilage regeneration: a review","volume":"16","author":"Hiruthyaswamy","year":"2025","journal-title":"Bioengineered"},{"key":"2026062906164749300_sxag021-B4","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1001\/jama.2025.3471","article-title":"Metformin for knee osteoarthritis in patients with overweight or obesity: a randomized clinical trial","volume":"333","author":"Pan","year":"2025","journal-title":"JAMA"},{"key":"2026062906164749300_sxag021-B5","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s13287-025-04233-5","article-title":"The role of adipose-derived stem cells in knee osteoarthritis treatment: insights from a triple-blind clinical study","volume":"16","author":"Sajadi","year":"2025","journal-title":"Stem Cell Res Ther"},{"key":"2026062906164749300_sxag021-B6","doi-asserted-by":"publisher","first-page":"336","DOI":"10.2106\/JBJS.L.01329","article-title":"Restoration of articular cartilage","volume":"96","author":"Moran","year":"2014","journal-title":"J Bone Joint Surg Am"},{"key":"2026062906164749300_sxag021-B7","doi-asserted-by":"publisher","first-page":"6316","DOI":"10.3390\/ijms23116316","article-title":"Cartilage homeostasis and osteoarthritis","volume":"23","author":"Fujii","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026062906164749300_sxag021-B8","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.toxicon.2022.01.002","article-title":"Transforming growth factor-\u03b2 receptors mediates matrix degradation and abnormal hypertrophy in T-2 toxin-induced hypertrophic chondrocytes","volume":"207","author":"Zhang","year":"2022","journal-title":"Toxicon"},{"key":"2026062906164749300_sxag021-B9","doi-asserted-by":"publisher","first-page":"102100","DOI":"10.1016\/j.mtbio.2025.102100","article-title":"Immunomodulatory biomaterials for osteoarthritis: targeting inflammation and enhancing cartilage regeneration","volume":"34","author":"Zhao","year":"2025","journal-title":"Mater Today Bio"},{"key":"2026062906164749300_sxag021-B10","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.joca.2024.10.014","article-title":"Osteoarthritis year in review 2024: genetics, genomics, and epigenetics","volume":"33","author":"Boer","year":"2025","journal-title":"Osteoarthritis Cartilage"},{"key":"2026062906164749300_sxag021-B11","doi-asserted-by":"publisher","first-page":"10923","DOI":"10.1038\/s41467-024-55335-2","article-title":"GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression","volume":"15","author":"Shen","year":"2024","journal-title":"Nat Commun"},{"key":"2026062906164749300_sxag021-B12","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/s41413-025-00413-4","article-title":"SIRT3-PINK1-PKM2 axis prevents osteoarthritis via mitochondrial renewal and metabolic switch","volume":"13","author":"Deng","year":"2025","journal-title":"Bone Res"},{"key":"2026062906164749300_sxag021-B13","doi-asserted-by":"publisher","first-page":"6471","DOI":"10.7150\/thno.96723","article-title":"Mitochondrial transfer balances cell redox, energy and metabolic homeostasis in the osteoarthritic chondrocyte preserving cartilage integrity","volume":"14","author":"Court","year":"2024","journal-title":"Theranostics"},{"key":"2026062906164749300_sxag021-B14","doi-asserted-by":"publisher","first-page":"1102S","DOI":"10.1177\/19476035211063858","article-title":"Role of mitochondria in physiology of chondrocytes and diseases of osteoarthritis and rheumatoid arthritis","volume":"13","author":"Kan","year":"2021","journal-title":"Cartilage"},{"key":"2026062906164749300_sxag021-B15","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.joca.2021.10.009","article-title":"Mitochondrial quality control in cartilage damage and osteoarthritis: new insights and potential therapeutic targets","volume":"30","author":"Liu","year":"2022","journal-title":"Osteoarthritis Cartilage"},{"key":"2026062906164749300_sxag021-B16","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41419-024-07312-2","article-title":"Ferroptosis triggers mitochondrial fragmentation via Drp1 activation","volume":"16","author":"Pedrera","year":"2025","journal-title":"Cell Death Dis"},{"key":"2026062906164749300_sxag021-B17","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1080\/15548627.2024.2440843","article-title":"Endogenous interactomes of MFN1 and MFN2 provide novel insights into interorganelle communication and autophagy","volume":"21","author":"Gordaliza-Alaguero","year":"2025","journal-title":"Autophagy"},{"key":"2026062906164749300_sxag021-B18","doi-asserted-by":"publisher","first-page":"5996","DOI":"10.1038\/s41467-025-60933-9","article-title":"The loss of OPA1 accelerates intervertebral disc degeneration and osteoarthritis in aged mice","volume":"16","author":"Madhu","year":"2025","journal-title":"Nat Commun"},{"key":"2026062906164749300_sxag021-B19","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1186\/s12951-024-02517-1","article-title":"Chondrocyte-targeted exosome-mediated delivery of Nrf2 alleviates cartilaginous endplate degeneration by modulating mitochondrial fission","volume":"22","author":"Lin","year":"2024","journal-title":"J Nanobiotechnology"},{"key":"2026062906164749300_sxag021-B20","doi-asserted-by":"publisher","first-page":"2928","DOI":"10.7150\/thno.69533","article-title":"AdMSC-derived exosomes alleviate acute lung injury via transferring mitochondrial component to improve homeostasis of alveolar macrophages","volume":"12","author":"Xia","year":"2022","journal-title":"Theranostics"},{"key":"2026062906164749300_sxag021-B21","doi-asserted-by":"publisher","first-page":"104983","DOI":"10.1016\/j.yexmp.2025.104983","article-title":"Mitochondrial dysfunction in fibrotic diseases: research progress and MSC-exos therapy","volume":"143","author":"Zhang","year":"2025","journal-title":"Exp Mol Pathol"},{"key":"2026062906164749300_sxag021-B22","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1146\/annurev-biochem-013118-111902","article-title":"Exosomes","volume":"88","author":"Pegtel","year":"2019","journal-title":"Annu Rev Biochem"},{"key":"2026062906164749300_sxag021-B23","doi-asserted-by":"publisher","first-page":"114916","DOI":"10.1016\/j.intimp.2025.114916","article-title":"Exosomal miR-574-3p from adipose-derived mesenchymal stem modulates CRIM1\/BMPs signaling to restrain chondrocytes hypertrophy and inflammatory response in knee osteoarthritis","volume":"159","author":"Kang","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"2026062906164749300_sxag021-B24","doi-asserted-by":"crossref","first-page":"e70811","DOI":"10.1096\/fj.202501185R","article-title":"Adipose mesenchymal stem cells derived exosomes ameliorates KOA cartilage damage and inflammation by activation of PINK1-mediated mitochondrial autophagy","volume":"39","author":"Kang","year":"2025","journal-title":"FASEB J"},{"key":"2026062906164749300_sxag021-B25","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1186\/s13018-025-05742-y","article-title":"USP15-modified ADMSCs-Exo alleviates chondrocyte damage and effectively relieved osteoarthritis by inducing M2 polarization of macrophages through deubiquitinating FOXC1","volume":"20","author":"Liang","year":"2025","journal-title":"J Orthop Surg Res"},{"key":"2026062906164749300_sxag021-B26","doi-asserted-by":"publisher","first-page":"4683","DOI":"10.2147\/IJN.S420967","article-title":"Dental pulp stem cell-derived exosomes regulate anti-inflammatory and osteogenesis in periodontal ligament stem cells and promote the repair of experimental periodontitis in rats","volume":"18","author":"Qiao","year":"2023","journal-title":"Int J Nanomedicine"},{"key":"2026062906164749300_sxag021-B27","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1186\/s13287-020-01781-w","article-title":"Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis","volume":"11","author":"He","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"2026062906164749300_sxag021-B28","doi-asserted-by":"publisher","first-page":"155512","DOI":"10.1016\/j.phymed.2024.155512","article-title":"Shikonin suppresses rheumatoid arthritis by inducing apoptosis and autophagy via modulation of the AMPK\/mTOR\/ULK-1 signaling pathway","volume":"128","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"2026062906164749300_sxag021-B29","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/978-1-0716-4607-6_15","article-title":"Isolation of adipose-derived mesenchymal stromal\/stem cells","volume":"2938","author":"Athanasiadis","year":"2025","journal-title":"Methods Mol Biol"},{"key":"2026062906164749300_sxag021-B30","doi-asserted-by":"publisher","first-page":"213","DOI":"10.2217\/rme-2018-0161","article-title":"Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial","volume":"14","author":"Freitag","year":"2019","journal-title":"Regen Med"},{"key":"2026062906164749300_sxag021-B31","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s13287-023-03359-8","article-title":"Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial","volume":"14","author":"Sadri","year":"2023","journal-title":"Stem Cell Res Ther"},{"key":"2026062906164749300_sxag021-B32","doi-asserted-by":"publisher","first-page":"1532S","DOI":"10.1177\/1947603520951623","article-title":"Does the source of mesenchymal stem cell have an effect in the management of osteoarthritis of the knee? Meta-analysis of randomized controlled trials","volume":"13","author":"Jeyaraman","year":"2021","journal-title":"Cartilage"},{"key":"2026062906164749300_sxag021-B33","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1186\/s12967-025-06310-y","article-title":"Multi-omics analysis of synovial tissue and fluid reveals differentially expressed proteins and metabolites in osteoarthritis","volume":"23","author":"Ge","year":"2025","journal-title":"J Transl Med"},{"key":"2026062906164749300_sxag021-B34","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/s41580-024-00785-1","article-title":"Molecular mechanisms of mitochondrial dynamics","volume":"26","author":"T\u00e1bara","year":"2025","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026062906164749300_sxag021-B35","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1038\/s41586-025-08590-2","article-title":"Dual regulation of mitochondrial fusion by Parkin-PINK1 and OMA1","volume":"639","author":"Yamada","year":"2025","journal-title":"Nature"},{"key":"2026062906164749300_sxag021-B36","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/s41467-024-55758-x","article-title":"Mitochondria- and ER-associated actin are required for mitochondrial fusion","volume":"16","author":"Gatti","year":"2025","journal-title":"Nat Commun"},{"key":"2026062906164749300_sxag021-B37","doi-asserted-by":"publisher","first-page":"eadn8699","DOI":"10.1126\/scitranslmed.adn8699","article-title":"Epithelial OPA1 links mitochondrial fusion to inflammatory bowel disease","volume":"17","author":"Bao","year":"2025","journal-title":"Sci Transl Med"},{"key":"2026062906164749300_sxag021-B38","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.freeradbiomed.2025.07.025","article-title":"MITF promotes MFN2-dependent mitochondrial fusion to protect retinal pigment epithelial cells from mitochondrial damage","volume":"239","author":"Chen","year":"2025","journal-title":"Free Radic Biol Med"},{"key":"2026062906164749300_sxag021-B39","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/978-3-031-88361-3_3","article-title":"Mitochondrial quality control","volume":"1478","author":"Guan","year":"2025","journal-title":"Adv Exp Med Biol"},{"key":"2026062906164749300_sxag021-B40","doi-asserted-by":"publisher","first-page":"109349","DOI":"10.1016\/j.intimp.2022.109349","article-title":"Nodakenin attenuates cartilage degradation and inflammatory responses in a mice model of knee osteoarthritis by regulating mitochondrial Drp1\/ROS\/NLRP3 axis","volume":"113","author":"Yi","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"2026062906164749300_sxag021-B41","doi-asserted-by":"publisher","first-page":"110651","DOI":"10.1016\/j.intimp.2023.110651","article-title":"TRPV4-mediated mitochondrial dysfunction induces pyroptosis and cartilage degradation in osteoarthritis via the Drp1-HK2 axis","volume":"123","author":"Yan","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"2026062906164749300_sxag021-B42","doi-asserted-by":"publisher","first-page":"4892","DOI":"10.1038\/s41467-025-60037-4","article-title":"Chondrocyte fatty acid oxidation drives osteoarthritis via SOX9 degradation and epigenetic regulation","volume":"16","author":"Mei","year":"2025","journal-title":"Nat Commun"},{"key":"2026062906164749300_sxag021-B43","doi-asserted-by":"publisher","first-page":"115595","DOI":"10.1016\/j.biopha.2023.115595","article-title":"Geniposide stimulates autophagy by activating the GLP-1R\/AMPK\/mTOR signaling in osteoarthritis chondrocytes","volume":"167","author":"Huang","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"2026062906164749300_sxag021-B44","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.bbi.2022.02.015","article-title":"Sestrin2 overexpression attenuates osteoarthritis pain via induction of AMPK\/PGC-1\u03b1-mediated mitochondrial biogenesis and suppression of neuroinflammation","volume":"102","author":"Sun","year":"2022","journal-title":"Brain Behav Immun"},{"key":"2026062906164749300_sxag021-B45","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.3390\/biomedicines10071477","article-title":"The role of mitochondrial metabolism, AMPK-SIRT mediated pathway, LncRNA and microRNA in osteoarthritis","volume":"10","author":"Liu","year":"2022","journal-title":"Biomedicines"},{"key":"2026062906164749300_sxag021-B46","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1007\/s10565-025-10071-1","article-title":"Asperosaponin VI mitigates mitochondrial dysfunction and chondrocyte apoptosis in osteoarthritis by modulating the AMPK-SIRT3 pathway","volume":"41","author":"Qiao","year":"2025","journal-title":"Cell Biol Toxicol"},{"key":"2026062906164749300_sxag021-B47","doi-asserted-by":"publisher","first-page":"512","DOI":"10.3390\/antiox14050512","article-title":"Nitazoxanide modulates mitochondrial function and inflammatory metabolism in chondrocytes from patients with osteoarthritis via AMPK\/mTORC1 signaling","volume":"14","author":"Kim","year":"2025","journal-title":"Antioxidants (Basel)"}],"container-title":["Stem Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/stmcls\/advance-article-pdf\/doi\/10.1093\/stmcls\/sxag021\/68143801\/sxag021.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/44\/7\/sxag021\/68143801\/sxag021.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/44\/7\/sxag021\/68143801\/sxag021.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T10:16:55Z","timestamp":1782728215000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stmcls\/article\/doi\/10.1093\/stmcls\/sxag021\/8661469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":47,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,6,27]]}},"URL":"https:\/\/doi.org\/10.1093\/stmcls\/sxag021","relation":{},"ISSN":["1066-5099","1549-4918"],"issn-type":[{"value":"1066-5099","type":"print"},{"value":"1549-4918","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,4,22]]},"article-number":"sxag021"}}