{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:54:28Z","timestamp":1791543268863,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"56","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"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":["82302826"],"award-info":[{"award-number":["82302826"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["TGY24H060028"],"award-info":[{"award-number":["TGY24H060028"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Long\u2010term glucocorticoids (GCs) use induces glucocorticoids\u2010induced osteoporosis (GIOP), but the underlying mechanisms remain unclear. This study investigated the role of Parkin in regulating ACSL4\u2010mediated ferroptosis in GIOP and developed a bone\u2010targeted mRNA therapeutic strategy. Using dexamethasone (DEX)\u2010treated bone marrow mesenchymal stem cells (BMSCs) and a GIOP mouse model, we found that GCs induced typical ferroptosis in BMSCs. Parkin expression was significantly downregulated in GIOP models. Parkin knockdown exacerbated DEX\u2010induced lipid peroxidation, iron accumulation, and mitochondrial dysfunction, while inhibiting osteogenesis and promoting adipogenesis; Parkin overexpression reversed these phenotypes. Mechanistically, Parkin directly bound to ACSL4 and promoted its K48\u2010linked polyubiquitination and proteasomal degradation. Based on these findings, we constructed DSS6\u2010modified bone\u2010targeted lipid nanoparticles (LNPs) (Parkin\u2010LNP@DSS6), which efficiently encapsulated mRNA and exhibited excellent bone\u2010homing ability. Parkin\u2010LNP@DSS6 inhibited ferroptosis and restored osteogenic differentiation in vitro, and significantly improved bone microstructural parameters in GIOP mice. Transcriptome sequencing confirmed suppression of ferroptosis and fatty acid metabolism pathways. Collectively, this study reveals a novel mechanism by which Parkin inhibits BMSCs ferroptosis via K48 ubiquitination\u2010mediated degradation of ACSL4 to alleviate GIOP, and provides a promising bone\u2010targeted mRNA delivery strategy for GIOP and other ferroptosis\u2010related bone diseases.<\/jats:p>","DOI":"10.1002\/advs.76586","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:55:28Z","timestamp":1783943728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ubiquitination of ACSL4 by Parkin Suppresses Ferroptosis and Rescues Glucocorticoid\u2010Induced Bone Loss"],"prefix":"10.1002","volume":"13","author":[{"given":"Li\u2010jiang","family":"Han","sequence":"first","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010sen","family":"Miao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1969-9352","authenticated-orcid":false,"given":"Yi\u2010feng","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"},{"name":"Department of Orthopedics The First Affiliated Hospital of Ningbo University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010ting","family":"Tu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010zhe","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin\u2010Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing\u2010hao","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua\u2010lin","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan\u2010qi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010qiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4079-5289","authenticated-orcid":false,"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8582-4599","authenticated-orcid":false,"given":"Ai\u2010min","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"},{"name":"Department of Plastic and Aesthetic Surgery Nanfang Hospital Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7374-6506","authenticated-orcid":false,"given":"Jian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1663-4101","authenticated-orcid":false,"given":"Gang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4332-4553","authenticated-orcid":false,"given":"Chen","family":"Jin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Osteoporosis and Geriatric Bone Health of Wenzhou  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010200544010\u201000003"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2024.109440"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202414902"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.05.023"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201016883\u20109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198\u2010015\u20103381\u2010x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010025\u201008067\u2010y"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0860"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0718"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010024\u201005191\u2010x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202307388"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010024\u201001513\u20109"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.05.008"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.12.027"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0789"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2023.213738"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184331"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S433511"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c05632"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092177"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12081590"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120586"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.20960\/nh.212"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2024.2416070"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42646"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010024\u201003709\u20100"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S493001"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495\u2010025\u201002077\u20101"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2200554"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103194"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002533"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202303261"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76586","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.76586","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76586","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:24:17Z","timestamp":1791541457000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.76586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":32,"journal-issue":{"issue":"56","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/advs.76586"],"URL":"https:\/\/doi.org\/10.1002\/advs.76586","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]},"assertion":[{"value":"2026-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e76586"}}