{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T19:01:30Z","timestamp":1770058890735,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Sirtuin1 (Sirt1)\/forkhead box O1 (FoxO1) axis has been reported as a crucial regulator involved in chondral homeostasis of healthy or osteoarthritis (OA) cartilage. In our study, the aim is to investigate whether <jats:italic>dioscin<\/jats:italic> functions as an activator of Sirt1\/FoxO1 to protect against mechanical stress\u2010induced chondrocyte dysfunction in vitro and in vivo models.\u00a0HERB and PubChem databases were implemented to predict dioscin\u2010related gene targets. Cell and mouse models of OA were established to determine the pharmacological value of dioscin, a steroidal saponin. Cartilage loss in the knee joint was detected by Safranin O staining. Phosphorylation and nucleocytoplasmic shuttling of FoxO1 was observed in mechanical stress\u2010stimulated chondrocyte and anterior cruciate ligament transection\u2010induced cartilage injury. However, dioscin treatment repressed FoxO1 phosphorylation and cytoplasmic transfer and elevated Sirt1 protein expression. Dioscin treatment reversed mechanical stress\u2010induced growth inhibition and apoptosis of chondrocytes and improved cartilage degradation and bone loss in the epiphysis of the distal femur. Moreover, dioscin could maintain the normal phenotype of chondrocytes via mediating multiple gene expressions. Dioscin inhibited apoptosis and metabolic disorders in OA\u2010like chondrocytes via maintaining the transcriptional activity of FoxO1 and enhancing Sirt1 expression. Dioscin might be a potential Sirt1 activator providing a novel therapeutic schedule for the treatment of OA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbt.23212","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T06:40:32Z","timestamp":1663224032000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mechanical stress\u2010caused chondrocyte dysfunction and cartilage injury can be attenuated by dioscin via activating sirtuin1\/forkhead box O1"],"prefix":"10.1002","volume":"36","author":[{"given":"Shilin","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2083-6214","authenticated-orcid":false,"given":"Feng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.02.026"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.11.031"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.09.022"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201905977"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.05.003"},{"issue":"9","key":"e_1_2_8_7_1","first-page":"3930","volume":"8","author":"You M.","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092250"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.01.018"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3507"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1918673117"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan0746"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2005.04.006"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947603519847736"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28452"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.809822"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.11.004"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan0746"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.93"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2013.12.004"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8152373"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000481804"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183541"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01030"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13862"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2016.06.002"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1619-1_2"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14021"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1215-5_23"},{"key":"e_1_2_8_31_1","first-page":"11","volume":"10","author":"Liu X.","year":"2021","journal-title":"Cells"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15193"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2018.1526603"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.05.025"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2017056117"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15009"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004820"},{"issue":"1","key":"e_1_2_8_38_1","first-page":"237","volume":"39","author":"Fernandes J. C.","year":"2002","journal-title":"Biorheology"},{"issue":"4","key":"e_1_2_8_39_1","first-page":"5463","volume":"17","author":"Zhao L. R.","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"e_1_2_8_40_1","first-page":"5","volume":"39","author":"Deng Z.","year":"2019","journal-title":"Biosci. Rep."},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-016-0591-y"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24864"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21284"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202620"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601253R"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22859"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.10.020"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/10253890.2018.1501022"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.467"},{"key":"e_1_2_8_50_1","first-page":"17","volume":"20","author":"Wu Q.","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.009409"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.23212","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.23212","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.23212","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T13:04:11Z","timestamp":1692450251000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.23212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,14]]},"references-count":50,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/jbt.23212"],"URL":"https:\/\/doi.org\/10.1002\/jbt.23212","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,14]]},"assertion":[{"value":"2022-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23212"}}