{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:54:36Z","timestamp":1786978476884,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"publisher","award":["2022D01C565"],"award-info":[{"award-number":["2022D01C565"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bone is one of the most frequent sites for metastasis in breast cancer patients. Bone metastasis significantly reduces the survival time and the life quality of breast cancer patients. Germacrone (GM) can serve humans as an anti\u2010cancer and anti\u2010inflammation agent, but its effect on breast cancer\u2010induced osteolysis remains unclear. This study aims to investigate the functions and mechanisms of GM in alleviating breast cancer\u2010induced osteolysis. The effects of GM on osteoclast differentiation, bone resorption, F\u2010actin ring formation, and gene expression were examined in vitro. RNA\u2010sequencing and Western Blot were conducted to explore the regulatory mechanisms of GM on osteoclastogenesis. The effects of GM on breast cancer\u2010induced osteoclastogenesis, and breast cancer cell malignant behaviors were also evaluated. The in vivo efficacy of GM in the ovariectomy model and breast cancer bone metastasis model with micro\u2010CT and histomorphometry. GM inhibited osteoclastogenesis, bone resorption and F\u2010actin ring formation in vitro. Meanwhile, GM inhibited the expression of osteoclast\u2010related genes. RNA\u2010seq analysis and Western Blot confirmed that GM inhibited osteoclastogenesis via inhibition of MAPK\/NF\u2010\u03baB signaling pathways. The in vivo mouse osteoporosis model further confirmed that GM inhibited osteolysis. In addition, GM suppressed the capability of proliferation, migration, and invasion and promoted the apoptosis of MDA\u2010MB\u2010231 cells. Furthermore, GM could inhibit MDA\u2010MB\u2010231 cell\u2010induced osteoclastogenesis in vitro and alleviate breast cancer\u2010associated osteolysis in vivo human MDA\u2010MB\u2010231 breast cancer bone metastasis\u2010bearing mouse models. Our findings identify that GM can be a promising therapeutic agent for patients with breast cancer osteolytic bone metastasis.<\/jats:p>","DOI":"10.1002\/ptr.8195","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T10:39:25Z","timestamp":1711967965000},"page":"2860-2874","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Germacrone alleviates breast cancer\u2010associated osteolysis by inhibiting osteoclastogenesis via inhibition of\n                    <scp>MAPK<\/scp>\n                    \/\n                    <scp>NF\u2010\u03baB<\/scp>\n                    signaling pathways"],"prefix":"10.1002","volume":"38","author":[{"given":"Zhengjun","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaocheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Xiangya Hospital Central South University  Changsha 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