{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:29:59Z","timestamp":1786595399533,"version":"build-2736575974"},"reference-count":14,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"WKU-ISRG grant","award":["ISRG2023032"],"award-info":[{"award-number":["ISRG2023032"]}]},{"name":"WKU-ISRG grant","award":["ISRG2023027"],"award-info":[{"award-number":["ISRG2023027"]}]},{"name":"International Frontier Interdisciplinary Research Institute of Wenzhou-Kean University","award":["KY20250604000450"],"award-info":[{"award-number":["KY20250604000450"]}]},{"name":"Wenzhou-Kean University","award":["WB20220901000092"],"award-info":[{"award-number":["WB20220901000092"]}]},{"award":["WB20220901000092"],"award-info":[{"award-number":["WB20220901000092"]}],"id":[{"id":"https:\/\/ror.org\/05609xa16","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Excessive osteoclast formation is a key contributor to pathological bone loss in disorders such as osteoporosis and rheumatoid arthritis. Asarinin, a natural lignan, has not previously been examined in the context of osteoclast differentiation. Here, we investigated the anti-osteoclastogenic effects of asarinin using RANKL-stimulated RAW264.7 cells. Asarinin significantly suppressed TRAP-positive multinucleated osteoclast formation. Mechanistically, asarinin selectively inhibited RANKL-induced phosphorylation of p38 and ERK MAPKs, leading to reduced c-Fos expression and inhibition of NFATc1 activation. In addition, asarinin disrupted actin ring formation in mature osteoclasts. Collectively, these findings identify asarinin as a pathway-selective inhibitor of osteoclast differentiation, acting through a mechanism consistent with modulation of the p38\/ERK\u2013c-Fos\u2013NFATc1 signaling cascade while sparing parallel signaling pathways.<\/jats:p>","DOI":"10.3390\/ijms27167159","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:09:36Z","timestamp":1786435776000},"page":"7159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Asarinin Inhibits RANKL-Induced Osteoclast Differentiation by Targeting the p38\/ERK\u2013c-Fos\u2013NFATc1 Axis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3727-1618","authenticated-orcid":false,"given":"Lifang","family":"Zhang","sequence":"first","affiliation":[{"name":"Osteoimmunology & Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China"},{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxu","family":"Xie","sequence":"additional","affiliation":[{"name":"Osteoimmunology & Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China"},{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Bao","sequence":"additional","affiliation":[{"name":"Osteoimmunology & Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, 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Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farwa","family":"Basit","sequence":"additional","affiliation":[{"name":"Osteoimmunology & Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China"},{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yili","family":"Ding","sequence":"additional","affiliation":[{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA"},{"name":"Department of Chemistry, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2158-2631","authenticated-orcid":false,"given":"Mojtaba","family":"Tabandeh","sequence":"additional","affiliation":[{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA"},{"name":"Department of Chemistry, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0148-255X","authenticated-orcid":false,"given":"Vishwa","family":"Deepak","sequence":"additional","affiliation":[{"name":"Osteoimmunology & Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China"},{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA"},{"name":"International Frontier Interdisciplinary Research Institute (IFIRI) of Wenzhou-Kean University, Wenzhou 325060, China"},{"name":"Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou 325060, China"},{"name":"Zhejiang Bioinformatics International Science and Technology Cooperation Center, Wenzhou-Kean University, Wenzhou 325060, China"},{"name":"Zhejiang-Malaysia Joint Laboratory for Rare Medicinal Resources, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-pathmechdis-031521-040919","article-title":"Osteoclasts, Master Sculptors of Bone","volume":"18","author":"Veis","year":"2023","journal-title":"Annu. 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