{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T11:52:04Z","timestamp":1793793124022,"version":"4.6.1"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"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":["81672143"],"award-info":[{"award-number":["81672143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802247"],"award-info":[{"award-number":["81802247"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81902237"],"award-info":[{"award-number":["81902237"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004921","name":"Shanghai Jiao Tong University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008235","name":"School of Medicine","doi-asserted-by":"publisher","award":["DLY201616"],"award-info":[{"award-number":["DLY201616"]}],"id":[{"id":"10.13039\/100008235","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Osteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol\u2010induced ONFH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K\/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol\u2010induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti\u2010osteogenesis of alcohol partly <jats:italic>via<\/jats:italic> PI3K\/AKT pathway and retard the promotion of alcohol\u2010induced adipogenesis <jats:italic>via<\/jats:italic> AMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol\u2010induced ONFH and substantially restore the bone volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrated that CPA ameliorated alcohol\u2010induced ONFH possibly <jats:italic>via<\/jats:italic> regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol\u2010induced ONFH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.12871","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T09:20:25Z","timestamp":1593422425000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Chrysophanic acid shifts the differentiation tendency of BMSCs to prevent alcohol\u2010induced osteonecrosis of the femoral head"],"prefix":"10.1111","volume":"53","author":[{"given":"Hongping","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9242-2486","authenticated-orcid":false,"given":"Youshui","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-1383(16)30835-X"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-018-4236-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/14397595.2014.932038"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0805786"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201902463RR"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70050"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100913-013132"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3928\/01477447-20080501-33"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1996.tb01095.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000150568.16133.3c"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000063602.67412.83"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2018.01.003"},{"key":"e_1_2_9_14_1","article-title":"The role of the subchondral layer in osteonecrosis of the femoral head: analysis based on HR\u2010QCT in comparison to MRI findings","volume":"284185118786070","author":"Kolb AR","year":"2018","journal-title":"Acta Radiol"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-018-0040-8"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.11.025"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000480181"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15103"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom9020068"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.13143"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00476"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/370530"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6082"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/452621"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-017-1986-7"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.24081"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24278"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/iep.12035"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14754"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19160"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.5435\/JAAOS-22-07-455"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2009.05.022"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-010-1292-x"},{"issue":"15","key":"e_1_2_9_34_1","first-page":"2766","article-title":"Key pathway to prevent the collapse of femoral head in osteonecrosis","volume":"19","author":"Gou WL","year":"2015","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063628"},{"issue":"6","key":"e_1_2_9_36_1","first-page":"1046","article-title":"Pathomorphological changes of bone marrow adipocytes in process of steroid\u2010associated osteonecrosis","volume":"6","author":"Sheng H","year":"2013","journal-title":"International journal of clinical and experimental pathology"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2015.99"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.04.020"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16075"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1168-2"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2014.03.059"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2016.03.013"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25423"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(01)00663-9"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.10.035"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31366-1"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008207.2014.941106"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2585-y"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.4161\/15548627.2014.981916"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5718(01)00150-4"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2011.08.003"}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcpr.12871","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.12871","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cpr.12871","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.12871","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T13:57:43Z","timestamp":1692453463000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.12871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,29]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1111\/cpr.12871"],"URL":"https:\/\/doi.org\/10.1111\/cpr.12871","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,29]]},"assertion":[{"value":"2020-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12871"}}