{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:14:12Z","timestamp":1791386052398,"version":"4.3.3"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T00:00:00Z","timestamp":1553040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY17C100002"],"award-info":[{"award-number":["LY17C100002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Current pharmacological intervention for the treatment of osteolytic bone diseases such as osteoporosis focuses on the prevention of excessive osteoclastic bone resorption but does not enhance osteoblast\u2010mediated bone formation. In our study, we have shown that 4\u2010iodo\u20106\u2010phenylpyrimidine (4\u2010IPP), an irreversible inhibitor of macrophage migration inhibitory factor (MIF), can inhibit receptor activator of NF\u2010\u03baB ligand (RANKL)\u2010induced osteoclastogenesis and potentiate osteoblast\u2010mediated mineralization and bone nodule formation\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Mechanistically, 4\u2010IPP inhibited RANKL\u2010induced p65 phosphorylation and nuclear translocation by preventing the interaction of MIF with thioredoxin\u2010interacting protein\u2014p65 complexes. This led to the suppression of late osteoclast marker genes such as nuclear factor of activated T cells cytoplasmic 1, resulting in impaired osteoclast formation. In contrast, 4\u2010IPP potentiated osteoblast differentiation and mineralization also through the inhibition of the p65\/NF\u2010\u03baB signaling cascade. In the murine model of pathologic osteolysis induced by titanium particles, 4\u2010IPP protected against calvarial bone destruction. Similarly, in the murine model of ovariectomy\u2010induced osteoporosis, 4\u2010IPP treatment ameliorated the bone loss associated with estrogen deficiency by reducing osteoclastic activities and enhancing osteoblastic bone formation. Collectively, these findings provide evidence for the pharmacological targeting of MIF for the treatment of osteolytic bone disorders.\u2014Zheng, L., Gao, J., Jin, K., Chen, Z., Yu, W., Zhu, K., Huang, W., Liu, F., Mei, L., Lou, C., He, D. Macrophage migration inhibitory factor (MIF) inhibitor 4\u2010IPP suppresses osteoclast formation and promotes osteoblast differentiation through the inhibition of the NF\u2010\u03baB signaling pathway. FASEB J. 33, 7667\u20137683 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802364rr","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T18:26:27Z","timestamp":1553106387000},"page":"7667-7683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Macrophage migration inhibitory factor (MIF) inhibitor 4\u2010IPP suppresses osteoclast formation and promotes osteoblast differentiation through the inhibition of the NF\u2010\u03baB signaling pathway"],"prefix":"10.1096","volume":"33","author":[{"given":"Lin","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangtao","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangwei","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengwei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Lishui Hospital of Zhejiang University\u2014the Fifth Affiliated Hospital of Wenzhou University\u2014Lishui Central Hospital Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.153.3731.80"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.56.1.72"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.6.1895"},{"key":"e_1_2_8_5_1","first-page":"235","article-title":"Migration inhibitory factor expression in experimentally induced endotoxemia","volume":"150","author":"Bacher M.","year":"1997","journal-title":"Am. J. Pathol."},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1997.0276"},{"key":"e_1_2_8_7_1","first-page":"98","article-title":"Studies on the production of MIF and mitogenic factor using highly purified human T and B lymphocytes","volume":"6","author":"Rocklin R. E.","year":"1975","journal-title":"Rheumatology"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.08.020"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1567"},{"key":"e_1_2_8_10_1","article-title":"Adrenomedullin protects Leydig cells against lipopolysaccharide-induced oxidative stress and inflammatory reaction via MAPK\/NF-\u03baB signalling pathways","volume":"7","author":"Hu W.","year":"2017","journal-title":"Sci. Rep."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200106)44:6<1273::AID-ART219>3.0.CO;2-8"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.104.038331"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.25.18100"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/35041591"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.10.1375"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-016-0326-x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.01.038"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.06.028"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-010-1385-0"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.060310"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2854"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1996.d01-751.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-994966"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2012.10.006"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106020200"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6227"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-15-0299"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2013.1944"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djw131"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3334"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.141"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1805"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2017.03.007"},{"key":"e_1_2_8_34_1","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1359\/jbmr.040913","article-title":"Regulation of human osteoclast differentiation by thioredoxin binding protein-2 and redox-sensitive signaling","volume":"19","author":"Aitken C. J.","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2011.12.010"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.159"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.133"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1593"},{"key":"e_1_2_8_40_1","doi-asserted-by":"crossref","DOI":"10.1186\/ar2110","article-title":"Cells of the synovium in rheumatoid arthritis. Osteoclasts","volume":"9","author":"Schett G.","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"e_1_2_8_41_1","article-title":"Lycorine suppresses RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced osteoporosis and titanium particle-induced osteolysis in vivo","volume":"5","author":"Chen S.","year":"2015","journal-title":"Sci. Rep."},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20150151"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32850-7"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1513724"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2016.098"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39844"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3279"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2011.09.005"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.11.015"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/377068a0"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703265200"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi991352p"},{"key":"e_1_2_8_53_1","article-title":"Inhibitory effect of purpurogallin on osteoclast differentiation in vitro through the downregulation of c-Fos and NFATc1","volume":"19","author":"Kim K.","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.663518"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40175"}],"updated-by":[{"DOI":"10.1096\/fj.201802364rrerr","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2019,12,22]],"date-time":"2019-12-22T00:00:00Z","timestamp":1576972800000}}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201802364RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201802364RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201802364RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:16:59Z","timestamp":1761700619000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201802364RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,20]]},"references-count":54,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1096\/fj.201802364RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.201802364rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,20]]},"assertion":[{"value":"2018-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}