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Cytisine is a quinolizidine alkaloid that comes from seeds or other plants of the Leguminosae (Fabaceae) family. Cytisine has been shown several potential pharmacological functions. However, its effects on PMOP remain unknown. This study designed to explore whether Cytisine is able to suppress RANKL\u2010induced osteoclastogenesis and prevent the bone loss induced by oestrogen deficiency in ovariectomized (OVX) mice. In this study, we investigated the effect of Cytisine on RAW 264.7 cells and bone marrow monocytes (BMMs) derived osteoclast culture system in vitro and observed the effect of Cytisine on ovariectomized (OVX) mice model to imitate postmenopausal osteoporosis in vivo. We found that Cytisine inhibited F\u2010actin ring formation and tartrate\u2010resistant acid phosphatase (TRAP) staining in dose\u2010dependent ways, as well as bone resorption by pit formation assays. For molecular mechanism, Cytisine suppressed RANK\u2010related trigger RANKL by phosphorylation JNK\/ERK\/p38\u2010MAPK, I\u03baB\u03b1\/p65\u2010NF\u2010\u03baB, and PI3K\/AKT axis and significantly inhibited these signalling pathways. However, the suppression of PI3K\u2010AKT\u2010NFATc1 axis was rescued by AKT activator SC79. Meanwhile, Cytisine inhibited RANKL\u2010induced RANK\u2010TRAF6 association and RANKL\u2010related gene and protein markers such as NFATc1, Cathepsin K, MMP\u20109 and TRAP. Our study indicated that Cytisine could suppress bone loss in OVX mouse through inhibited osteoclastogenesis. All data provide the evidence that Cytisine may be a promising agent in the treatment of osteoclast\u2010related diseases such as osteoporosis.<\/jats:p>","DOI":"10.1111\/jcmm.15622","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T14:00:26Z","timestamp":1597327226000},"page":"10112-10127","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL\u2010induced osteoclastogenesis"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-7560","authenticated-orcid":false,"given":"Zhi","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Pudong Hospital Fudan University Pudong Medical Center Huinan Town China"},{"name":"Department of Orthopaedic Surgery Zhangye People's Hospital affiliated to Hexi University Zhangye City 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