{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:06:16Z","timestamp":1789268776857,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22277076"],"award-info":[{"award-number":["22277076"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009564","name":"Health and Family Planning Commission of Sichuan Province","doi-asserted-by":"publisher","award":["ZY(2021\u20102023)\u20100208"],"award-info":[{"award-number":["ZY(2021\u20102023)\u20100208"]}],"id":[{"id":"10.13039\/501100009564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Forsythia suspensa<\/jats:italic> tea is a popular traditional Chinese medicine decoction for its healthy and therapeutic benefits. However, its effects in bone metabolism were not clear. In recent study, we uncovered anti\u2010osteoclastogenesis property of Phillygenin (Phi), a compound abundant in <jats:italic>Forsythia suspensa<\/jats:italic> leaves, and aimed to investigate the effect and mechanism of Phi on bone metabolism in vivo and in vitro. Lipopolysaccharides\u2010induced murine calvaria osteolysis and ovariectomy\u2010induced bone loss animal models were used to identify the bone\u2010protective effect of Phi in vivo and micro\u2010CT, pQCT, and TRAP staining were applied. We used CCK8, TUNEL, BrdU, and TRAP staining to evaluate the efficacy of Phi on the proliferation and formation of OCs in primary mBMMs. RNA sequence, activity\u2010based protein profiling, molecular docking, G\u2010LISA, and WB were used to inspect the target and underlying mechanism of Phi's actions in mBMMs. We found Phi significantly inhibited bone resorption in vivo and inhibited mBMMs osteoclastogenesis in vitro. Ras homolog gene family member A (RhoA) was identified as the direct target of Phi. It counteracted the effects of RhoA activator and acted as a RhoA inhibitor. By targeting RhoA, Phi modulated Rho\u2010associated coiled\u2010coil containing protein kinase 1 (ROCK1) activity and regulated its downstream NF\u2010\u03baB\/NFATc1\/c\u2010fos pathway. Furthermore, Phi depressed the disassembling of F\u2010actin ring through cofilin and myosin1a. Our findings provided Phi as a potential option for treating bone loss diseases by targeting RhoA and highlighted the importance of <jats:italic>F. suspensa<\/jats:italic> as a preventive approach in bone disorders.<\/jats:p>","DOI":"10.1002\/ptr.8074","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T16:29:26Z","timestamp":1708014566000},"page":"1863-1881","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Phillygenin prevents osteoclast differentiation and bone loss by targeting RhoA"],"prefix":"10.1002","volume":"38","author":[{"given":"Jiahui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Chemical Biology Core Facility, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences University of Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renhao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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