{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:51:16Z","timestamp":1773697876772,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,10,20]],"date-time":"2018-10-20T00:00:00Z","timestamp":1539993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702186"],"award-info":[{"award-number":["81702186"]}],"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":["81501910"],"award-info":[{"award-number":["81501910"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1107828"],"award-info":[{"award-number":["1107828"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1027932"],"award-info":[{"award-number":["1027932"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Excessive osteoclast formation and function are considered as the main causes of bone lytic disorders such as osteoporosis and osteolysis. Therefore, the osteoclast is a potential therapeutic target for the treatment of osteoporosis or other osteoclast\u2010related diseases. Helvolic acid (HA), a mycotoxin originally isolated from <jats:italic>Aspergillus fumigatus<\/jats:italic> , has been discovered as an effective broad\u2010spectrum antibacterial agent and has a wide range of pharmacological properties. Herein, for the first time, HA was demonstrated to be capable of significantly inhibiting receptor activator of nuclear factor\u2010\u03baB ligand (RANKL)\u2010induced osteoclastogenesis and bone resorption in vitro by suppressing nuclear factor of activated T cells 1 (NFATc1) activation. This inhibition was followed by the dramatically decreased expression of NFATc1\u2010targeted genes including \n<jats:italic>Ctr<\/jats:italic> (encoding calcitonin receptor), \n<jats:italic>Acp5<\/jats:italic> (encoding tartrate\u2010resistant acid phosphatase [TRAcP]), \n<jats:italic>Ctsk<\/jats:italic> (encoding cathepsin K), \n<jats:italic>Atp6v0d2<\/jats:italic> (encoding the vacuolar H+ ATPase V0 subunit d2 [V\u2010ATPase\u2010d2]) and \n<jats:italic>Mmp9<\/jats:italic> (encoding matrix metallopeptidase 9) which are osteoclastic\u2010specific genes required for osteoclast formation and function. Mechanistically, HA was shown to greatly attenuate multiple upstream pathways including extracellular signal\u2010regulated kinase (ERK) phosphorylation, c\u2010Fos signaling, and intracellular Ca\n<jats:sup>2+<\/jats:sup> oscillation, but had little effect on nuclear factor\u2010\u03baB (NF\u2010\u03baB) activation. In addition, HA also diminished the RANKL\u2010induced generation of intracellular reactive oxygen species. Taken together, our study indicated HA effectively suppressed RANKL\u2010induced osteoclast formation and function. Thus, we propose that HA can be potentially used in the development of a novel drug for osteoclast\u2010related bone diseases.<\/jats:p>","DOI":"10.1002\/jcp.27385","type":"journal-article","created":{"date-parts":[[2018,10,20]],"date-time":"2018-10-20T11:00:17Z","timestamp":1540033217000},"page":"6477-6488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Helvolic acid attenuates osteoclast formation and function via suppressing RANKL\u2010induced NFATc1 activation"],"prefix":"10.1002","volume":"234","author":[{"given":"Kai","family":"Chen","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, University of Western Australia Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1032-6330","authenticated-orcid":false,"given":"Yu","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Western Australia Perth Western Australia Australia"},{"name":"School of Physical Education and Sports Science, South China Normal University Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Western Australia Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dezhi","family":"Song","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Western Australia Perth Western Australia Australia"},{"name":"Research Centre for Regenerative Medicine, Guangxi Medical University Nanning Guangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinmin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Research Centre for Regenerative Medicine, Guangxi Medical University Nanning Guangxi China"},{"name":"Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University  Guangxi China"},{"name":"International Joint Laboratory on Regeneration of Bone and Soft Tissues, Guangxi Medical University  Guangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Western Australia Perth Western Australia Australia"},{"name":"Department of Biomedical Materials Science Third Military Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhao","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Western Australia Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Western Australia Perth Western Australia Australia"},{"name":"Department of Spine Surgery Xiangya Hospital, Central South University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Western Australia Perth Western Australia Australia"},{"name":"Melbourne Medical School, University of Melbourne Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Tickner","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Western Australia Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2021-8309","authenticated-orcid":false,"given":"Jiake","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Western Australia Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,20]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2170"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35711"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/36593"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.12.1741"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051150"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4773"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.06.001"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26126"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2005.12.012"},{"key":"e_1_2_7_1_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.18.2412"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.260"},{"key":"e_1_2_7_1_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8480174"},{"key":"e_1_2_7_1_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1910"},{"key":"e_1_2_7_1_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00007.2006"},{"key":"e_1_2_7_1_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2974"},{"key":"e_1_2_7_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.01.002"},{"key":"e_1_2_7_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.10.066"},{"key":"e_1_2_7_1_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2007-0237"},{"key":"e_1_2_7_1_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505815200"},{"key":"e_1_2_7_1_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/16852"},{"key":"e_1_2_7_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2012.03.021"},{"key":"e_1_2_7_1_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804314"},{"key":"e_1_2_7_1_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-09-3662"},{"key":"e_1_2_7_1_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2016.1266353"},{"key":"e_1_2_7_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2004.12.004"},{"key":"e_1_2_7_1_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408795200"},{"key":"e_1_2_7_1_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313973200"},{"key":"e_1_2_7_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2006.03.009"},{"key":"e_1_2_7_1_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00821.x"},{"key":"e_1_2_7_1_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786410801972813"},{"key":"e_1_2_7_1_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.10.536"},{"key":"e_1_2_7_1_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/21501203.2014.892905"},{"key":"e_1_2_7_1_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(99)00061-2"},{"key":"e_1_2_7_1_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.5520340206"},{"key":"e_1_2_7_1_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(93)90233-Y"},{"key":"e_1_2_7_1_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25304"},{"key":"e_1_2_7_1_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.10.001"},{"key":"e_1_2_7_1_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00369-6"},{"key":"e_1_2_7_1_41_1","doi-asserted-by":"publisher","DOI":"10.1358\/dnp.2004.17.1.829022"},{"key":"e_1_2_7_1_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.6.3373-3382.2004"},{"key":"e_1_2_7_1_43_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121626"},{"key":"e_1_2_7_1_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00332.x"},{"key":"e_1_2_7_1_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2009.08.004"},{"key":"e_1_2_7_1_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370216668051"},{"key":"e_1_2_7_1_47_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.11.2178"},{"key":"e_1_2_7_1_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2008.11.007"},{"key":"e_1_2_7_1_49_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.050324"},{"key":"e_1_2_7_1_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2771"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.27385","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.27385","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.27385","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.27385","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T17:07:40Z","timestamp":1747328860000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.27385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,20]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/jcp.27385"],"URL":"https:\/\/doi.org\/10.1002\/jcp.27385","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,20]]},"assertion":[{"value":"2018-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}