{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T02:44:56Z","timestamp":1789267496714,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Experimental Path"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Excessive endoplasmic reticulum (ER) stress can lead to apoptosis of nucleus pulposus cells (NPCs), a hallmark of intervertebral disc degeneration (IVDD). Our study aimed to determine whether bone marrow mesenchymal stem cells (BMSCs\u2010exos) alleviate ER stress\u2010related NPC apoptosis through the delivery of miR\u2010221\u20103p. Human NPCs were stimulated by advanced glycation end products (AGEs) for 24\u2009h to construct a cellular model of ER stress. Exosomes were isolated from BMSCs transfected with miR\u2010NC and miR\u2010221\u20103p inhibitor and co\u2010cultured together with AGEs in NPCs. MiR\u2010221\u20103p expression in NPCs was detected by reverse transcription quantitative real\u2010time polymerase chain reaction (RT\u2010qPCR). The protein levels of ER stress and apoptosis markers and nuclear factor erythroid 2 p45\u2010related factor 2 (Nrf2)\/heme oxygenase 1 (HO\u20101) pathway\u2010related molecules in NPCs were measured by western blotting and immunofluorescence staining. The Nrf2 agonist tert\u2010butylhydroquinone (TBHQ) was used to verify whether exosomal miR\u2010221\u20103p affected ER stress\u2010mediated apoptosis by regulating the Nrf2\/HO\u20101 pathway. MiR\u2010221\u20103p expression was decreased in AGEs\u2010stimulated NPCs, while co\u2010culture with BMSCs\u2010exos rescued such a decline. AGEs\u2010induced reduction in NPC viability and elevation in cell apoptosis and ER stress were overturned by BMSCs\u2010exos treatment, whereas miR\u2010221\u20103p knockdown further antagonized these effects of BMSCs\u2010exos. MiR\u2010221\u20103p knockdown reversed the enhancement of BMSCs\u2010exos on Nrf2 and HO\u20101 levels and Nrf2 nuclear translocation in AGEs\u2010induced NPCs. Importantly, TBHQ abrogated the promotion of Exos\u2010miR\u2010221\u20103p inhibitor on ER stress and apoptosis in NPCs. BMSCs\u2010exos reduced ER stress\u2010mediated apoptosis in NPCs by promoting the Nrf2\/HO\u20101 pathway through delivering miR\u2010221\u20103p.<\/jats:p>","DOI":"10.1111\/iep.70008","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T15:05:28Z","timestamp":1762527928000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exosomal\n                    <scp>miR<\/scp>\n                    \u2010221\u20103p derived from bone marrow mesenchymal stem cells alleviates endoplasmic reticulum stress\u2010mediated apoptosis in nucleus pulposus cells via the Nrf2\/\n                    <scp>HO<\/scp>\n                    \u20101 signalling pathway"],"prefix":"10.1111","volume":"106","author":[{"given":"Gang","family":"Xu","sequence":"first","affiliation":[{"name":"Yangzhou University  Yangzhou China"},{"name":"Department of Orthopedics The First Affiliated Hospital of Bengbu Medical 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