{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:06:29Z","timestamp":1790006789928,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) is a degenerative joint disease, for which effective disease\u2010modifying therapies remain lacking. Here, we report yam\u2010derived nanovesicles (YDNVs) as a plant\u2010derived exosome\u2010like nanoplatform with intrinsic therapeutic activity for OA treatment. YDNVs exhibited typical nanoscale vesicular characteristics and were efficiently internalized by chondrocytes via clathrin\u2010mediated endocytosis. Through enzymatic pretreatment and multi\u2010omics analyses, RNA\u2010particularly microRNAs (miRNAs)\u2010was identified as the primary bioactive component mediating their anti\u2010inflammatory effects. Mechanistic studies further confirmed that aof\u2010miR168a directly binds to the 3\u2032 untranslated regions of TLR4 and TRAF6, thereby suppressing downstream inflammatory signaling. To enhance targeting and therapeutic efficacy, a cartilage\u2010targeting peptide\u2010modified system (YDNVs\u2010CAP) was engineered via membrane insertion of a cholesterol\u2010anchored conjugate. This modification significantly improved cellular uptake, cartilage targeting, and intra\u2010articular retention. Functionally, YDNVs\u2010CAP effectively alleviated inflammation, oxidative stress, and extracellular matrix degradation in vitro, and markedly attenuated OA progression in a destabilization of the medial meniscus (DMM) mouse model. Collectively, this study establishes an RNA\u2010mediated therapeutic mechanism for plant\u2010derived nanovesicles and highlights YDNVs\u2010CAP as a promising biomimetic nanoplatform for disease\u2010modifying OA therapy.<\/jats:p>","DOI":"10.1002\/smll.75914","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:45:53Z","timestamp":1790005553000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Yam\u2010Derived Vesicles Alleviate Osteoarthritis via miRNA\u2010Mediated Suppression of the TLR4\u2013TRAF6 Signaling Axis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2515-7245","authenticated-orcid":false,"given":"Junyan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The Third Xiangya Hospital Central South University  Changsha China"},{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Third Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9108-6270","authenticated-orcid":false,"given":"Lingyu","family":"Su","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6667-5169","authenticated-orcid":false,"given":"Zhirou","family":"Lin","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8073-9312","authenticated-orcid":false,"given":"Chong","family":"Liu","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1413-7804","authenticated-orcid":false,"given":"Shilong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Xiangya Hospital Central South University  Changsha China"},{"name":"The Hunan Institute of Pharmacy Practice and Clinical Research  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3883-2833","authenticated-orcid":false,"given":"Hong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Hunan Provincial Key Laboratory of Multi\u2010omics and Artificial Intelligence of Cardiovascular Diseases The First Affiliated Hospital Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-6716","authenticated-orcid":false,"given":"Chengxian","family":"Guo","sequence":"additional","affiliation":[{"name":"Center of Clinical Pharmacology The Third Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Hunan Provincial Key Laboratory of Multi\u2010omics and Artificial Intelligence of Cardiovascular Diseases The First Affiliated Hospital Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0428-3928","authenticated-orcid":false,"given":"Zhaoqian","family":"Liu","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha China"},{"name":"Department of Cardiology Hunan Provincial Key Laboratory of Multi\u2010omics and Artificial Intelligence of Cardiovascular Diseases The First Affiliated Hospital Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-661X","authenticated-orcid":false,"given":"Wenhu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6711-4251","authenticated-orcid":false,"given":"Qi","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Third Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4661-6762","authenticated-orcid":false,"given":"Qianfei","family":"Cui","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/annals\u201024\u201001249"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2025.08.015"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010021\u201000710\u2010y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010024\u201002138\u2010w"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010025\u201000594\u20106"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002556\u20106"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2026.03.015"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123098"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.209"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2020.01.011"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead493"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.125"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.11.057"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2023.106733","article-title":"Current understanding of Plant\u2010Derived Exosome\u2010Like Nanoparticles in Regulating the Inflammatory Response and Immune System Microenvironment","volume":"190","author":"Yi Q.","year":"2023","journal-title":"Pharmacological Research"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2021.05.006"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.114108"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.113664"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010024\u201002313\u2010x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.64"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.10.032"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","first-page":"8040","DOI":"10.1021\/acsnano.4c16085","article-title":"Microalgae\u2010Derived Extracellular Vesicles Synergize With Herbal Hydrogel for Energy Homeostasis in Osteoarthritis Treatment","volume":"19","author":"Liang F.","year":"2025","journal-title":"ACS Nano"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.S526287"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s44403-025-00022-3","article-title":"Yam as Functional Food: Bioactive Properties, Health Benefits, and Applications","volume":"2","author":"Tareen M. B. K.","year":"2025","journal-title":"Food, Nutrition and Health"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2013.04.031"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.106024"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods12091772"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2010.09.003"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1423\u20100127\u201021\u201030"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.01.071"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073719"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26154480"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010021\u201000730\u20101"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2018.10.002"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223\u2010014\u20109917\u20109"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010025\u201003602\u20109"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11071806"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.05.017"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.04.009"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.03.006"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201021184\u20105"}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.75914","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/smll.75914","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.75914","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:45:54Z","timestamp":1790005554000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.75914"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":40,"alternative-id":["10.1002\/smll.75914"],"URL":"https:\/\/doi.org\/10.1002\/smll.75914","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"assertion":[{"value":"2026-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e75914"}}