{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:10:30Z","timestamp":1787015430662,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"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":["80212076"],"award-info":[{"award-number":["80212076"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aseptic prosthetic loosening due to wear particle\u2013induced inflammatory osteolysis is the main cause of failure for artificial joint replacement. The inflammatory response and the production of pro\u2010osteoclastic factors lead to elevation of osteoclast formation and excessive activity results in extensive bone destruction around the bone\u2010implant interface. Here we showed that Nepetin, a natural bioactive flavonoid with proven anti\u2010inflammatory and anti\u2010proliferative properties, potently inhibited RANKL\u2010induced osteoclast differentiation, formation and bone resorption in vitro, and protected mice against the deleterious effects of titanium particle\u2013induced calvarial osteolysis in vivo. Mechanistically, Nepetin attenuated RANKL\u2010induced activation of NF\u2010\u03baB and MAPK signalling pathways and TRAF6\u2010dependent ubiquitination of Beclin 1 which is necessary for the induction of autophagy. In brief, our study demonstrates the potential therapeutic application of Nepetin against osteoclast\u2010mediated osteolytic diseases.<\/jats:p>","DOI":"10.1111\/jcmm.16055","type":"journal-article","created":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T23:20:31Z","timestamp":1604272831000},"page":"14366-14380","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Nepetin inhibits osteoclastogenesis by inhibiting RANKL\u2010induced activation of NF\u2010\u03baB and MAPK signalling pathway, and autophagy"],"prefix":"10.1111","volume":"24","author":[{"given":"Binxiang","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Dajiangdong Hospital Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2166-2666","authenticated-orcid":false,"given":"Xiaohe","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pathology Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajing","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghua","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32344-4"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302202"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/5214501","article-title":"Atypical mesenchymal stromal cell responses to topographic modifications of titanium biomaterials indicate cytoskeletal\u2010 and genetic plasticity\u2010based heterogeneity of cells","volume":"2019","author":"Khan MR","year":"2019","journal-title":"Stem Cells Int"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02963"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4TB01005A"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01408"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1105-7"},{"key":"e_1_2_9_9_1","first-page":"84","article-title":"Osteoclasts in health and disease","volume":"17","author":"Lerner UH","year":"2019","journal-title":"Pediatr Endocrinol Rev"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000238813.95035.1b"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.MCHD-0011-2015"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.12.1741"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540500137669"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.8.1015"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3756"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax3769"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-019-2691-5"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.11.083"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2011.05.040"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22139"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28857"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.25467"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202009200"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8122091"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1503\/cjs.003711"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2170"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3883"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8070932"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.04.003"},{"key":"e_1_2_9_30_1","first-page":"47","article-title":"Denosumab\u2010associated peri\u2010implant atypical femur fracture: a case report","volume":"78","author":"Dupaix JP","year":"2019","journal-title":"Hawaii J Health Soc Welf"},{"key":"e_1_2_9_31_1","first-page":"965","article-title":"Cytotoxic activity of nepetin, a flavonoid from Eupatorium ballotaefolium HBK","volume":"59","author":"Militao GC","year":"2004","journal-title":"Pharmazie"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01248"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2017.0225"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-018-1490-7"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610701200"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0185-4"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27071"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-019-0058-7"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.08.016"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.07.018"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66947"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.16055","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.16055","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.16055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T05:31:55Z","timestamp":1723095115000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.16055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":40,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1111\/jcmm.16055"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.16055","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11]]},"assertion":[{"value":"2020-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}