{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:48:31Z","timestamp":1791920911248,"version":"4.3.4"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T00:00:00Z","timestamp":1571270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31870895, 31171135"],"award-info":[{"award-number":["31870895, 31171135"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2019.01188","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T08:27:30Z","timestamp":1571300850000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Phillyrin Attenuates Osteoclast Formation and Function and Prevents LPS-Induced Osteolysis in Mice"],"prefix":"10.3389","volume":"10","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuli","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1080\/08916930701694543","article-title":"Role of the NF-kappaB axis in immune modulation of osteoclasts and bone loss","volume":"41","author":"Abuamer","year":"2008","journal-title":"Autoimmunity"},{"key":"B2","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/jcb.10503","article-title":"Phosphatidylinositol 3-kinase coordinately activates the MEK\/ERK and AKT\/NFkappaB pathways to maintain osteoclast survival","volume":"89","author":"Anne","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1084\/jem.20051150","article-title":"Autoamplification of NFATc1 expression determines its essential role in bone homeostasis","volume":"202","author":"Asagiri","year":"2005","journal-title":"J. Exp. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2082","DOI":"10.1359\/jbmr.2001.16.11.2082","article-title":"Adherent endotoxin on orthopedic wear particles stimulates cytokine production and osteoclast differentiation","volume":"16","author":"Bi","year":"2010","journal-title":"J. Bone Miner. Metab."},{"key":"B5","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1242\/jcs.028217","article-title":"The JNK-dependent CaMK pathway restrains the reversion of committed cells during osteoclast differentiation","volume":"121","author":"Chang","year":"2008","journal-title":"J. Cell Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1080\/00498254.2016.1193262","article-title":"Effects of phillyrin and forsythoside a on rat cytochrome P450 activities in vivo and in vitro","volume":"47","author":"Cheng","year":"2017","journal-title":"Xenobiotica"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4317","DOI":"10.1242\/jcs.00082","article-title":"JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms","volume":"115","author":"David","year":"2002","journal-title":"J. Cell Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/8756-3282(85)90337-0","article-title":"Effect of sodium fluoride, calcium, phosphate, and vitamin D2 on trabecular bone balance and remodeling in osteoporotics","volume":"6","author":"Eriksen","year":"1985","journal-title":"Bone"},{"key":"B10","doi-asserted-by":"publisher","first-page":"11951","DOI":"10.1002\/jcp.27888","article-title":"Scutellarein inhibits RANKL-induced osteoclast formation in vitro and prevents LPS-induced bone loss in vivo","volume":"234","author":"Fu","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0736-0266(01)00070-5","article-title":"The role of osteoclast differentiation in aseptic loosening","volume":"20","author":"Greenfield","year":"2010","journal-title":"J. Orthop. Res."},{"key":"B12","first-page":"96","article-title":"Safety of osteoporosis treatment with sodium fluoride, calcium phosphate and vitamin D","volume":"13","author":"Hasling","year":"1987","journal-title":"Miner. Electrolyte Metab."},{"key":"B13","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1002\/jcb.21167","article-title":"Molecular analysis of RANKL-independent cell fusion of osteoclast-like cells induced by TNF-alpha, lipopolysaccharide, or peptidoglycan","volume":"101","author":"Hitoshi","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1128\/MCB.01075-15","article-title":"The transcriptional modulator Ifrd1 regulates osteoclast differentiation through enhancing NF-\u03baB\/NFATc1 pathway","volume":"36","author":"Iezaki","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1172\/JCI200419657","article-title":"Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation","volume":"114","author":"Ikeda","year":"2004","journal-title":"J. Clin. Invest."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1359\/jbmr.2001.16.9.1593","article-title":"Tumor necrosis factor alpha\u2013induced osteoclastogenesis requires tumor necrosis factor receptor\u2013associated factor 6","volume":"16","author":"Kaji","year":"2010","journal-title":"J. Bone Miner. Metab."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3574","DOI":"10.4049\/jimmunol.166.5.3574","article-title":"Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors","volume":"166","author":"Kikuchi","year":"2001","journal-title":"J. Immunol."},{"key":"B18","first-page":"444","article-title":"Skin Anti-aging effect of Forsythia viridissima L. extract","volume":"21","author":"Kim","year":"2006","journal-title":"Korean J. Biotechnol. Bioeng."},{"key":"B19","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1055\/s-0034-1368614","article-title":"Phillyrin, a natural lignan, attenuates tumor necrosis factor \u03b1\u2013mediated insulin resistance and lipolytic acceleration in 3T3-L1 adipocytes","volume":"80","author":"Kong","year":"2014","journal-title":"Planta Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.intimp.2017.07.003","article-title":"Psoralidin suppresses osteoclastogenesis in BMMs and attenuates LPS-mediated osteolysis by inhibiting inflammatory cytokines","volume":"51","author":"Kong","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"B21","first-page":"32","article-title":"Antibacterial constituents of the unripe fruit of Forsythia suspensa (Thunb.) Vahl","volume":"13","author":"Kuang","year":"1988","journal-title":"Zhong Yao Tong Bao"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/304830","article-title":"Chemical constituents from the fruits of Forsythia suspensa and their antimicrobial activity","volume":"2014","author":"Kuo","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"B23","doi-asserted-by":"publisher","first-page":"235","DOI":"10.7150\/ijbs.13814","article-title":"Selective regulation of MAPK signaling mediates RANKL-dependent osteoclast differentiation","volume":"12","author":"Lee","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1177\/154405910608500703","article-title":"Bone remodeling in post-menopausal osteoporosis","volume":"85","author":"Lerner","year":"2006","journal-title":"J. Dent. Res."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113698","article-title":"Jatrorrhizine hydrochloride suppresses RANKL-induced osteoclastogenesis and protects against wear particle-induced osteolysis","volume":"19","author":"Li","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1016\/j.ajpath.2015.06.017","article-title":"MAGED1 is a negative regulator of bone remodeling in mice","volume":"185","author":"Liu","year":"2015","journal-title":"Am. J. Pathol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1002\/jcp.26517","article-title":"Carnosic acid inhibits inflammation response and joint destruction on osteoclasts, fibroblast-like synoviocytes, and collagen-induced arthritis rats","volume":"185","author":"Liu","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/srep40487","article-title":"Osteoclastic miR-214 targets TRAF3 to contribute to osteolytic bone metastasis of breast cancer","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"40418","DOI":"10.1039\/C7RA06302D","article-title":"Phillygenin attenuates inflammatory responses and influences glucose metabolic parameters by inhibiting Akt activity","volume":"7","author":"Liu","year":"2017","journal-title":"Rsc Adv."},{"key":"B30","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":"Masataka","year":"2007","journal-title":"Bone"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1007\/BF01743376","article-title":"Bacterially induced bone destruction: mechanisms and misconceptions","volume":"64","author":"Nair","year":"1996","journal-title":"Infect. Immun."},{"key":"B32","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.bone.2004.04.023","article-title":"Lipopolysaccharide stimulates expression of osteoprotegerin and receptor activator of NF-kappa B ligand in periodontal ligament fibroblasts through the induction of interleukin-1 beta and tumor necrosis factor-alpha","volume":"35","author":"Naohisa","year":"2004","journal-title":"Bone"},{"key":"B33","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s00011-014-0731-7","article-title":"Forsythin inhibits lipopolysaccharide-induced inflammation by suppressing JAK-STAT and p38 MAPK signalings and ROS production","volume":"63","author":"Pan","year":"2014","journal-title":"Inflamm. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1211\/jpp.60.2.0016","article-title":"Antioxidant and antibacterial activity of two compounds (forsythiaside and forsythin) isolated from Forsythia suspensa","volume":"60","author":"Qu","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1007\/s12272-016-0775-z","article-title":"Protective effects of phillyrin against influenza a virus in vivo","volume":"39","author":"Qu","year":"2016","journal-title":"Arch. Pharm. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1002\/jcb.20256","article-title":"Etiology of paget\u2019s disease and osteoclast abnormalities","volume":"93","author":"Reddy","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"B37","first-page":"276","article-title":"RANKL and OPG in inflammatory arthritis and periprosthetic osteolysis","volume":"4","author":"Ritchlin","year":"2004","journal-title":"J. Musculoskeletal. Neuronal. Interaction"},{"key":"B38","first-page":"ch3","volume-title":"Osteoclast Biology and Bone Resorption.","author":"Rosen","year":"2013"},{"key":"B39","doi-asserted-by":"publisher","first-page":"371","DOI":"10.5483\/BMBRep.2002.35.4.371","article-title":"TAK1-dependent activation of AP-1 and c-Jun N-terminal kinase by receptor activator of NF-kappaB","volume":"35","author":"Soo Woong","year":"2002","journal-title":"J. Biochem. Mol. Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s00774-008-0026-6","article-title":"Inhibition of the classical NF-kappaB pathway prevents osteoclast bone-resorbing activity","volume":"27","author":"Soysa","year":"2009","journal-title":"J. Bone Miner. Metab."},{"key":"B41","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1196\/annals.1402.071","article-title":"The role of NFAT in osteoclast formation","volume":"1116","author":"Takayanagi","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s007740300021","article-title":"Signal transduction pathways regulating osteoclast differentiation and function","volume":"21","author":"Tanaka","year":"2003","journal-title":"J. Bone Miner. Metab."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1007\/s10571-014-0091-4","article-title":"Protective effects of phillyrin on H2O 2-induced oxidative stress and apoptosis in PC12 cells","volume":"34","author":"Teng","year":"2014","journal-title":"Cell. Mol. Neurobiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2839","DOI":"10.1056\/NEJMra040952","article-title":"Osteopetrosis","volume":"351","author":"Tolar","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.jep.2017.08.040","article-title":"Phytochemistry, pharmacology, quality control and future research of Forsythia suspensa (Thunb.) Vahl: a review","volume":"210","author":"Wang","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1359\/jbmr.2002.17.7.1211","article-title":"Dual modulation of osteoclast differentiation by lipopolysaccharide","volume":"17","author":"Wei","year":"2010","journal-title":"J. Bone Miner. Metab. Off. J. Am. Soc. Bone Miner. Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.fitote.2013.06.003","article-title":"Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of MAPK and NF-\u03baB activation in acute lung injury mice","volume":"90","author":"Wei-Ting","year":"2013","journal-title":"Fitoterapia"},{"key":"B48","doi-asserted-by":"publisher","first-page":"17812","DOI":"10.1002\/jcp.28408","article-title":"Daphnetin attenuates LPS-induced osteolysis and RANKL mediated osteoclastogenesis through suppression of ERK and NFATc1 pathways","volume":"234","author":"Wu","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"3105","DOI":"10.1210\/endo.143.8.8954","article-title":"p38 MAPK-mediated signals are required for inducing osteoclast differentiation but not for osteoclast function","volume":"143","author":"Xiaotong","year":"2002","journal-title":"Endocrinology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"18245","DOI":"10.1074\/jbc.M610701200","article-title":"NF-kappa B p50 and p52 regulate receptor activator of NF-kappa B ligand (RANKL) and tumor necrosis factor\u2013induced osteoclast precursor differentiation by activating c-Fos and NFATc1","volume":"282","author":"Yamashita","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B51","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/BF02911031","article-title":"Study on anti-senile and anti-oxidative activities of Forsythia suspense leaves tea","volume":"26","author":"Yang","year":"2004","journal-title":"Acta Nutrimenta Sinica"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1158\/0008-5472.CAN-04-1687","article-title":"Elevated serum levels of stromal-derived factor-1alpha are associated with increased osteoclast activity and osteolytic bone disease in multiple myeloma patients","volume":"65","author":"Zannettino","year":"2005","journal-title":"Cancer Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.biomaterials.2016.10.038","article-title":"Macrophage integrins modulate response to ultra-high molecular weight polyethylene particles and direct particle-induced osteolysis","volume":"115","author":"Zaveri","year":"2017","journal-title":"Biomaterials"},{"key":"B54","doi-asserted-by":"publisher","first-page":"16732","DOI":"10.1074\/jbc.M212473200","article-title":"CpG oligodeoxynucleotides modulate the osteoclastogenic activity of osteoblasts via Toll-like receptor 9","volume":"278","author":"Zou","year":"2003","journal-title":"J. Biol. Chem."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.01188\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T08:27:32Z","timestamp":1571300852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.01188\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,17]]},"references-count":54,"alternative-id":["10.3389\/fphar.2019.01188"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2019.01188","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,17]]},"article-number":"1188"}}