{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:31:26Z","timestamp":1788517886210,"version":"build-2803163510"},"reference-count":9,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020716","name":"Wenzhou-Kean University","doi-asserted-by":"publisher","award":["ISRG2023032"],"award-info":[{"award-number":["ISRG2023032"]}],"id":[{"id":"10.13039\/100020716","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020716","name":"Wenzhou-Kean University","doi-asserted-by":"publisher","award":["ISRG2023027"],"award-info":[{"award-number":["ISRG2023027"]}],"id":[{"id":"10.13039\/100020716","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Excessive osteoclast activity underlies bone-destructive diseases including osteoporosis and rheumatoid arthritis. RANKL-induced NF-\u03baB signaling represents a critical pathway driving osteoclastogenesis. Here, we report that methyl carnosate, a naturally occurring diterpene from rosemary, inhibits RANKL-induced osteoclastogenesis with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 1.2\u00a0\u03bcM (95% CI: 0.9521\u20131.372\u00a0\u03bcM) and displays greater potency than its parent compound, carnosic acid. Promoter\u2013reporter analysis further indicates attenuation of RANKL-induced NF-\u03baB activity, consistent with downstream suppression of NFATc1 mRNA expression. These findings identify methyl carnosate as a promising pharmacological candidate for the development of bone-protective therapeutics.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1825049","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:08:20Z","timestamp":1780466900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Methyl carnosate, a carnosic acid derivative, attenuates osteoclastogenesis via modulation of RANKL-induced NF-\u03baB activity"],"prefix":"10.3389","volume":"17","author":[{"given":"Lifang","family":"Zhang","sequence":"first","affiliation":[{"name":"Osteoimmunology and Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University","place":["Wenzhou, Zhejiang, China"]},{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University","place":["Union, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxu","family":"Xie","sequence":"additional","affiliation":[{"name":"Osteoimmunology and Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University","place":["Wenzhou, Zhejiang, China"]},{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University","place":["Union, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Bao","sequence":"additional","affiliation":[{"name":"Osteoimmunology and Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University","place":["Wenzhou, Zhejiang, China"]},{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University","place":["Union, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojtaba","family":"Tabandeh","sequence":"additional","affiliation":[{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University","place":["Union, NJ, United States"]},{"name":"Department of Chemistry, College of Science, Mathematics and Technology, Wenzhou-Kean University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwa","family":"Deepak","sequence":"additional","affiliation":[{"name":"Osteoimmunology and Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University","place":["Wenzhou, Zhejiang, China"]},{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University","place":["Union, NJ, United States"]},{"name":"International Frontier Interdisciplinary Research Institute (IFIRI) of Wenzhou-Kean University","place":["Wenzhou, Zhejiang, China"]},{"name":"Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University","place":["Wenzhou, Zhejiang, China"]},{"name":"Zhejiang Bioinformatics International Science and Technology Cooperation Center, Wenzhou-Kean University","place":["Wenzhou, Zhejiang, China"]},{"name":"Zhejiang-Malaysia Joint Laboratory For Rare Medicinal Resources, Wenzhou-Kean University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.bone.2006.09.023","article-title":"The molecular understanding of osteoclast differentiation","volume":"40","author":"Asagiri","year":"2007","journal-title":"Bone"},{"key":"B2","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1177\/1934578X1300800402","article-title":"Methyl carnosate, an antibacterial diterpene isolated from Salvia officinalis leaves","volume":"8","author":"Climati","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e2201490119","DOI":"10.1073\/pnas.2201490119","article-title":"IFT80 negatively regulates osteoclast differentiation via association with Cbl-b to disrupt TRAF6 stabilization and activation","volume":"119","author":"Deepak","year":"2022","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2951","DOI":"10.1021\/jf960068r","article-title":"Antioxidant activity of carnosic acid and methyl carnosate in bulk oils and oil-in-water emulsions","volume":"44","author":"Huang","year":"1996","journal-title":"J. Agric. Food Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"117600","DOI":"10.1016\/j.bone.2025.117600","article-title":"Treating osteoporosis with denosumab or bisphosphonates in the long term: facts, uncertainties and assumptions. A narrative review by the clinical action group of the european calcified tissue society (ECTS)","volume":"200","author":"Naciu","year":"2025","journal-title":"Bone"},{"key":"B6","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/s12276-024-01157-7","article-title":"Unraveling the intricacies of osteoclast differentiation and maturation: insight into novel therapeutic strategies for bone-destructive diseases","volume":"56","author":"Takegahara","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1007\/s00109-017-1553-1","article-title":"Carnosic acid attenuates RANKL-induced oxidative stress and osteoclastogenesis via induction of Nrf2 and suppression of NF-kappaB and MAPK signalling","volume":"95","author":"Thummuri","year":"2017","journal-title":"J. Mol. Med. Berl."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1038\/s41418-019-0484-5","article-title":"Dual targeting of SREBP2 and ERRalpha by carnosic acid suppresses RANKL-mediated osteoclastogenesis and prevents ovariectomy-induced bone loss","volume":"27","author":"Zheng","year":"2020","journal-title":"Cell Death Differ."},{"key":"B9","doi-asserted-by":"publisher","first-page":"116540","DOI":"10.1016\/j.bone.2022.116540","article-title":"Cytokine-mediated immunomodulation of osteoclastogenesis","volume":"164","author":"Zhou","year":"2022","journal-title":"Bone"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1825049\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:08:21Z","timestamp":1780466901000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1825049\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":9,"alternative-id":["10.3389\/fphar.2026.1825049"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1825049","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"article-number":"1825049"}}