{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:49:21Z","timestamp":1791654561976,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172479"],"award-info":[{"award-number":["82172479"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study addresses osteoarthritis (OA), in which dysregulated chondrocyte cholesterol homeostasis and cellular senescence contribute to cartilage degeneration, by developing an inflammation\u2010responsive injectable QCG hydrogel for local delivery of miR\u2010106a\u2010enriched M2 macrophage\u2010derived small extracellular vesicles (sEVs). The QCG hydrogel was constructed from quaternized chitosan (QCS) and 4\u2010carboxyphenylboronic acid\u2010gelatin (CPBA\u2010gelatin) and loaded with miR\u2010106a\u2010enriched M2\u2010sEVs (QCG@sEV\u2010miR\u2010106a). M2\u2010sEVs were isolated by differential ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and vesicle\u2010associated protein markers. High\u2010throughput miRNA profiling and chondrocyte RNA sequencing identified miR\u2010106a as a candidate regulatory molecule, and RNF128 was confirmed as a direct target by dual\u2010luciferase reporter assay. Functional experiments showed that miR\u2010106a suppresses RNF128, thereby promoting chondrocyte proliferation and extracellular matrix synthesis while attenuating senescence. Exploratory proteomic screening suggested RNF128\u2010associated changes in cholesterol\u2010 and lysosome\u2010related processes, whereas independent molecular and functional assays demonstrated that RNF128 promotes LXR\u03b1 ubiquitination and proteasome\u2010dependent degradation, suppresses LXR signaling, and disrupts cholesterol homeostasis. In a destabilization of the medial meniscus (DMM)\u2010induced OA rat model, QCG@sEV\u2010miR\u2010106a showed ROS\u2010responsive release, prolonged intra\u2010articular retention for up to 22\u00a0days, reduced cartilage degeneration and matrix loss, improved pain\u2010related behaviors, and favorable short\u2010term biocompatibility. Together, these findings support a local biomaterial delivery strategy in which miR\u2010106a\u2010mediated RNF128 inhibition preserves LXR signaling and cholesterol homeostasis to attenuate OA\u2010associated chondrocyte senescence.<\/jats:p>","DOI":"10.1002\/jev2.70386","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:12:49Z","timestamp":1791652369000},"source":"Crossref","is-referenced-by-count":0,"title":["M2 Macrophage\u2010Derived Small Extracellular Vesicle miR\u2010106a\u2010Loaded QCG Hydrogel Targets the RNF128\u2010LXR Pathway to Reprogram Chondrocyte Cholesterol Metabolism for Osteoarthritis Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Baozhe","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Shengjing Hospital of China Medical University  Shenyang 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