{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:25:11Z","timestamp":1787066711199,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023QH517"],"award-info":[{"award-number":["ZR2023QH517"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Glucocorticoid\u2010induced osteonecrosis of the femoral head (GC\u2010ONFH) represents a devastating complication of steroid therapy, primarily driven by osteoblast apoptosis and impaired osteogenesis. Although selenium (Se) is renowned for its potent bone\u2010protective properties, its therapeutic potential, and specific mechanisms in GC\u2010ONFH remain largely unexplored and thus require further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To assess the therapeutic effectiveness of oral selenium supplementation in GC\u2010ONFH, a rat model of GC\u2010ONFH was utilized. The rats were randomly allocated into three groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096 per group): (1) Control group, (2) Methylprednisolone sodium succinate (MPS) group, and (3) Se group. The intervention was carried out for 4\u2009weeks. In\u00a0vitro experiments utilized primary rat osteoblasts and MC3T3\u2010E1 cells to elucidate the mechanisms through which selenium mitigates dexamethasone (DEX)\u2010induced alterations in cell proliferation, apoptosis, and osteogenic differentiation. The assessments were conducted using micro\u2010CT and histomorphometry, CCK\u20108 assays and flow cytometry, as well as RT\u2013qPCR, Western blotting, and immunofluorescence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Selenium supplementation effectively prevented trabecular collapse and significantly reduced the number of empty lacunae in rats with GC\u2010ONFH. Specifically, an optimal dose of 10\u2009\u03bcmol Se successfully reversed the damage induced by DEX, including the restoration of cell proliferation, suppression of apoptosis, and rescue of osteogenic activity. Mechanistically, Se counteracts the DEX\u2010induced suppression of phosphorylated phosphatidylinositol 3\u2010kinase (p\u2010PI3K), phosphorylated protein kinase B (p\u2010AKT), and phosphorylated glycogen synthase kinase 3\u03b2 (GSK3\u03b2) (p\u2010GSK3\u03b2), thereby activating the PI3K\/AKT\/GSK3\u03b2 signaling pathway, which promotes cell proliferation, inhibits apoptosis, and enhances osteogenesis in osteoblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Selenium can activate the PI3K\/AKT\/GSK3\u03b2 pathway, reverse DEX\u2010induced hypoproliferation and apoptosis, restore osteogenic capacity, prevent trabecular collapse, and attenuate GC\u2010ONFH in rat models. Our findings demonstrate that selenium supplementation can be regarded as a clinically applicable strategy for impeding the progression of GC\u2010ONFH in at\u2010risk patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/os.70191","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T02:46:23Z","timestamp":1763520383000},"page":"3456-3467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Selenium Attenuates Dexamethasone\u2010Induced Osteoblast Dysfunction and Prevents Femoral Head Osteonecrosis via\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>GSK3\u03b2<\/scp>\n                    Pathway Activation"],"prefix":"10.1111","volume":"17","author":[{"given":"Sun","family":"Xuecheng","sequence":"first","affiliation":[{"name":"Clinical School\/College of Orthopedics Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4198-7177","authenticated-orcid":false,"given":"Chen","family":"Changjun","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma","family":"Xiaojie","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Surgery, Shandong Provincial Qianfoshan Hospital Clinical Medical College of Shandong University of Traditional Chinese Medicine  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shufeng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9061-289X","authenticated-orcid":false,"given":"Zhang","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8932-3110","authenticated-orcid":false,"given":"Xinlong","family":"Ma","sequence":"additional","affiliation":[{"name":"Clinical School\/College of Orthopedics Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-020-1565-3"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.3c01539"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S367214"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surge.2020.11.007"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150265"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2021.2015798"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/JSA.0000000000000187"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101574"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejendo\/lvac004"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2217\/rme.14.67"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pri.1536"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-05795-5"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.17450"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.17219\/acem\/152150"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871530320999200817114817"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/09636897221082687"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0293530"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.13319"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202201159"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61452-9"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202401620"},{"issue":"6","key":"e_1_2_11_23_1","article-title":"The Role of Trace Elements and Minerals in Osteoporosis","volume":"13","author":"Skalny A. V.","year":"2023","journal-title":"A Review of Epidemiological and Laboratory Findings. Biomolecules"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S285233"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678-4685-gmb-2019-0153"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2023.02.004"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18385"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.4c04199"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113855"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.12622"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2024.117074"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.2217\/rme-2021-0169"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2012.04.011"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9208035"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.729909"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11132104"},{"issue":"1","key":"e_1_2_11_37_1","first-page":"206","article-title":"Knockdown of Ski Decreases Osteosarcoma Cell Proliferation and Migration by Suppressing the PI3K\/Akt Signaling Pathway","volume":"56","author":"Zhao X.","year":"2020","journal-title":"International Journal of Oncology"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.11.103"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.14740\/wjon1702"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.11.017"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-019-2002-x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-021-10006-0"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2025.114598"},{"issue":"1","key":"e_1_2_11_44_1","first-page":"113","article-title":"Dok5 Regulates Proliferation and Differentiation of Osteoblast via Canonical Wnt\/\u03b2\u2010Catenin Signaling","volume":"22","author":"Xu L.","year":"2022","journal-title":"Journal of Musculoskeletal & Neuronal Interactions"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116399"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01907"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1088\/1748-605X\/ad38ac"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2021-0401"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano12111850"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2025.02.001"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/09636897221086965"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103268"}],"container-title":["Orthopaedic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/os.70191","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T02:15:28Z","timestamp":1765246528000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/os.70191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,18]]},"references-count":51,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/os.70191"],"URL":"https:\/\/doi.org\/10.1111\/os.70191","archive":["Portico"],"relation":{},"ISSN":["1757-7853","1757-7861"],"issn-type":[{"value":"1757-7853","type":"print"},{"value":"1757-7861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,18]]},"assertion":[{"value":"2025-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}