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Increased osteoclast numbers and bone resorption activity are the main factors contributing to bone loss\u2013related diseases such as osteoporosis. Therefore, modulating the formation and function of osteoclasts is critical for the effective treatment of osteolysis and osteoporosis. Kavain is the active ingredient extracted from the root of the kava plant, which possesses known anti\u2010inflammatory properties. However, the effects of kavain on osteoclastogenesis and bone resorption remain unclear. In this study, we found that kavain inhibits receptor activator of nuclear factor\u2010\u03baB ligand (RANKL)\u2013induced osteoclast differentiation and fusion using tartrate\u2010resistant acid phosphatase staining and immunofluorescence. Furthermore, kavain inhibited bone resorption performed by osteoclasts. Using reverse transcription\u2010polymerase chain reaction and western blot analysis, we found that kavain downregulates the expression of osteoclast marker genes, such as nuclear factor of activated T cells, cytoplasmic 1 (\n                    <jats:italic>Nfatc1<\/jats:italic>\n                    ), v\u2010atpase d2 (\n                    <jats:italic>Atp6v0d2<\/jats:italic>\n                    ), dendrocyte expressed seven transmembrane protein (\n                    <jats:italic>Dcstamp<\/jats:italic>\n                    ), matrix metallopeptidase 9 (\n                    <jats:italic>Mmp9<\/jats:italic>\n                    ), cathepsin K (\n                    <jats:italic>Ctsk<\/jats:italic>\n                    ), and\n                    <jats:italic>Acp5<\/jats:italic>\n                    . Additionally, kavain repressed RANKL\u2010induced calcium oscillations, nuclear factor of activated T cells activation, and mitogen\u2010activated protein kinase phosphorylation, while leaving NF\u2010\u03baB unaffected. We found no effects of kavain on either osteoblast proliferation or differentiation. Besides, kavain inhibited bone loss in ovariectomized mice by suppressing osteoclastogenesis. Collectively, these data suggest a potential use for kavain as a candidate drug for the treatment of osteolytic diseases.\n                  <\/jats:p>","DOI":"10.1002\/jcp.26893","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T02:55:56Z","timestamp":1533610556000},"page":"789-801","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Modulating calcium\u2010mediated NFATc1 and mitogen\u2010activated protein kinase deactivation underlies the inhibitory effects of kavain on osteoclastogenesis and bone resorption"],"prefix":"10.1002","volume":"234","author":[{"given":"Qiang","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Spine Surgery Xiangya Hospital, Central South University  Changsha China"},{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The 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":"Bo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Affiliate Hospital, School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangxiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery Chinese People\u2019s Liberation Army 66325 Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Tickner","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renxiang","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology Institute of Functional Biomolecules, Nanjing University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qile","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery Xiangya Hospital, Central South University  Changsha China"}],"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 The University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,4]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12784"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2016.01.024"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2014.06.017"},{"issue":"12","key":"e_1_2_7_1_6_1","first-page":"1593","article-title":"Signaling pathways governing osteoblast proliferation, differentiation and function","volume":"24","author":"Chau J. 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