{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:54:21Z","timestamp":1789386861223,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873993"],"award-info":[{"award-number":["81873993"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We investigated the role of astragaloside IV (AS\u2010IV) in preventing glucocorticoid\u2010induced avascular necrosis of the femoral head (ANFH) and the underlying molecular mechanisms. Network pharmacology was used to predict the molecular targets of AS\u2010IV. Molecular dynamic simulations were performed to explore the binding mechanism and interaction mode between AS\u2010IV and Akt. Rat models of glucocorticoid\u2010induced ANFH with AS\u2010IV intervention were established, and osteogenesis, angiogenesis, apoptosis and oxidative stress were evaluated before and after blocking the PI3K\/Akt pathway with LY294002. The effects of glucocorticoid and AS\u2010IV on bone marrow mesenchymal stem cells and human umbilical vein endothelial cells incubated with and without LY294002 were determined. Downregulated p\u2010Akt expression could be detected in the femoral heads of glucocorticoid\u2010induced ANFH patients and rats. AS\u2010IV increased trabecular bone integrity and vessel density of the femoral head in the model rats. AS\u2010IV increased Akt phosphorylation and upregulated osteogenesis\u2010, angiogenesis\u2010, apoptosis\u2010 and oxidative stress\u2010related proteins and mRNA and downregulated Bax, cleaved caspase\u20103 and cytochrome c levels. AS\u2010IV promoted human umbilical vein endothelial cell migration, proliferation and tube formation ability; bone marrow mesenchymal stem cell proliferation; and osteogenic differentiation under glucocorticoid influence. AS\u2010IV inhibited apoptosis. LY294002 inhibited these effects. AS\u2010IV prevented glucocorticoid\u2010induced ANFH by promoting osteogenesis and angiogenesis via the Akt\/Runx2 and Akt\/HIF\u20101\u03b1\/VEGF pathways, respectively, and suppressing apoptosis and oxidative stress via the Akt\/Bad\/Bcl\u20102 and Akt\/Nrf2\/HO\u20101 pathways, respectively.<\/jats:p>","DOI":"10.1111\/cpr.13485","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T03:54:31Z","timestamp":1682481271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Effects of astragaloside\n                    <scp>IV<\/scp>\n                    on glucocorticoid\u2010induced avascular necrosis of the femoral head via regulating Akt\u2010related pathways"],"prefix":"10.1111","volume":"56","author":[{"given":"Haojie","family":"Shan","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuli","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhao","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Shanghai Fengxian Central Hospital Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyang","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongtai","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojun","family":"Cao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaolai","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zubin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-4907","authenticated-orcid":false,"given":"Xiaowei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24541"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-05-643601"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2015.08.006"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2017.11.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.20.00847"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-015-3061-7"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108746"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1426-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.17450"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23008"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.16951"},{"issue":"3","key":"e_1_2_8_13_1","first-page":"3751","article-title":"Salidroside inhibits steroid\u2010induced avascular necrosis of the femoral head via the PI3K\/Akt signaling pathway: in vitro and in vivo studies","volume":"17","author":"Xue XH","year":"2018","journal-title":"Mol Med Rep"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/15476278.2019.1633869"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0FO00497A"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.112852"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0798-6"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/315850"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8424326"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12232"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.04.040"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2019.1569697"},{"issue":"2","key":"e_1_2_8_23_1","first-page":"830","article-title":"Astragaloside IV promotes the proliferation and migration of osteoblast\u2010like cells through the hedgehog signaling pathway","volume":"43","author":"Guo LH","year":"2019","journal-title":"Int J Mol Med"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.09.049"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.11.033"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104831"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109729"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3727\/096504018X15344989701565"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2022.113323"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaa379"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.9b00105"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.9b00055"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.38713"},{"issue":"3","key":"e_1_2_8_34_1","first-page":"244","article-title":"Astragaloside IV prevents obesity\u2010associated hypertension by improving pro\u2010inflammatory reaction and leptin resistance","volume":"41","author":"Jiang P","year":"2018","journal-title":"Mol Cells"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.12.032"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-016-0391-3"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15103"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.03.010"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106127"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2623"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29519"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.10.005"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.021"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2020.07.009"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2004.01.017"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.186"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1407-6"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053010"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3214196"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.8b01802"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01791-8"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.57681"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114350"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9782062"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11726"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2022.115535"}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.13485","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T09:11:39Z","timestamp":1699002699000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.13485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,26]]},"references-count":55,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/cpr.13485"],"URL":"https:\/\/doi.org\/10.1111\/cpr.13485","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,26]]},"assertion":[{"value":"2023-01-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13485"}}