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In consideration of the limitations of current therapeutic options for the treatment of postmenopausal osteoporosis, there is an urgent need to develop safer alternatives. Anacardic acid, a natural phenolic acid compound extracted from cashew nut shell, possesses potent antitumor and anti\u2010inflammatory effects and inhibits NF\u2010\u03baB signaling. However, its effect on osteoclasts remains unknown. This study reports the first evidence for the antiosteoclastogenic and antiresorptive effects of anacardic acid on bone marrow\u2013derived macrophage\u2013derived osteoclasts. Mechanistically, anacardic acid disrupts the phosphorylation of TGF\u2010\u03b2 activated kinase 1 and subsequently suppresses multiple receptor activator of NF\u2010\u03baB ligand\u2013induced signaling cascades, ultimately inhibiting the induction and activation of the crucial osteoclast transcriptional factor nuclear factor of activated T\u2010cell cytoplasmic 1. Consistent with cellular results\n                    <jats:italic>in vitro<\/jats:italic>\n                    , anacardic acid treatment improves bone density in the murine model of ovariectomy\u2010induced bone loss. Taken together, our study provides promising evidence for the therapeutic application of anacardic acid as a new potential pharmacological treatment for osteoporosis.\u2014Zhao, K., Jia, Y., Peng, J., Pang, C., Zhang, T., Han, W., Jiang, J., Lu, X., Zhu, J., Qian, Y. Anacardic acid inhibits RANKL\u2010induced osteoclastogenesis\n                    <jats:italic>in vitro<\/jats:italic>\n                    and prevents ovariectomy\u2010induced bone loss\n                    <jats:italic>in vivo<\/jats:italic>\n                    . FASEB J. 33, 9100\u20139115 (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.201802575rr","type":"journal-article","created":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T15:18:15Z","timestamp":1556896695000},"page":"9100-9115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Anacardic acid inhibits RANKL\u2010induced osteoclastogenesis\n                    <i>in vitro<\/i>\n                    and prevents ovariectomy\u2010induced bone loss\n                    <i>in vivo<\/i>"],"prefix":"10.1096","volume":"33","author":[{"given":"Kangxian","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Orthopedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"},{"name":"The Second Affiliated Hospital Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yewei","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shaoxing Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Regenerative Medicine Guangxi Medical University  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Pang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Regenerative Medicine Guangxi Medical University  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiqi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"},{"name":"Department of Orthopedics Shaoxing Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanyuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Medical College of Shaoxing University  Shaoxing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiling","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shaoxing Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"},{"name":"Department of Orthopedics Shaoxing Hospital Zhejiang University School of Medicine  Shaoxing China"},{"name":"The Second Affiliated Hospital Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Guangxi Key Laboratory of Regenerative Medicine Guangxi Medical University  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00113-015-0085-9"},{"key":"e_1_2_8_3_1","first-page":"527","article-title":"Physiopathology of osteoporosis: from risk factors analysis to treatment","volume":"29","author":"Del Puente A.","year":"2015","journal-title":"J. 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