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During osteoclast differentiation, osteoclasts take up a large amount of iron through transferrin receptor 1 (TfR1) mediated endocytosis of transferrin (Tf). Since iron\u2010dependent cleavage of endoperoxide bridge is of great importance for the antimalarial effects of artemisinin compounds, we raised a hypothesis that the cytotoxic effects of artemisinin compounds on osteoclasts were associated with enhanced iron uptake. In the present study, we found that Tf aggravated the inhibitory effects of artesunate (ART) on osteoclast viability and differentiation. ART induced the production of malondialdehyde (MDA) and 4\u2010hydroxynonenal (4\u2010HNE) in a dose\u2010dependent manner and led to the appearance of mitochondrial features of ferroptotic cells. TfR1 knockdown alleviated these cytotoxic effects of ART on osteoclasts. In addition, ART effectively prevented bone loss induced by iron overload. Our results indicate that ART inhibits iron\u2010uptake stimulated osteoclast differentiation by inducing ferroptosis. Artemisinin compounds are potential drugs for treating iron overload\u2010induced osteoporosis.<\/jats:p>","DOI":"10.1111\/bcpt.13817","type":"journal-article","created":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T14:54:19Z","timestamp":1669474459000},"page":"144-153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Artesunate inhibits osteoclast differentiation by inducing ferroptosis and prevents iron overload\u2010induced bone loss"],"prefix":"10.1111","volume":"132","author":[{"given":"Yuanqing","family":"Jin","sequence":"first","affiliation":[{"name":"Institute of Laboratory Animal Science Guizhou University of Traditional Chinese Medicine  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science Guizhou University of Traditional Chinese Medicine  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science Guizhou University of Traditional Chinese Medicine  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Yao","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science Guizhou University of Traditional Chinese Medicine  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science Guizhou University of Traditional Chinese Medicine  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penghai","family":"Qiao","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science Guizhou University of Traditional Chinese Medicine  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6117-3285","authenticated-orcid":false,"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science Guizhou University of Traditional Chinese Medicine  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2020.103358"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201017427\u20106"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.10.007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2771"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25907"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.69"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2012.06.001"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00685"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1910"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13492"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14277"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2019.06.007"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011\u2010019\u201001929\u20107"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010020\u201000441\u20101"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107658"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111380"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010020\u201000728\u20101"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1458143"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010019\u20100352\u20103"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201003996\u2010y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.12.011"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010020\u20100478\u20103"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.144188"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.04.002"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1692"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.10.005"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.09.023"}],"container-title":["Basic &amp; 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