{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:45:43Z","timestamp":1789587943870,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2014,11,28]],"date-time":"2014-11-28T00:00:00Z","timestamp":1417132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin,  a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory  effects on the ligand of the receptor activator of nuclear factor-\u03baB (RANKL)-induced osteoclastogenesis and revealed that the mechanism of action of naringenin, which inhibited osteoclastogenesis by suppression of the p38 signaling pathway. Through in vivo studies,  we proved that naringenin attenuated titanium particle-induced osteolysis in a mouse calvarial model. In general, we demonstrated that naringenin inhibited osteoclastogenesis via suppression of p38 signaling in vitro and attenuated titanium particle-induced osteolysis in vivo. This study also suggested that naringenin has significant potential for the treatment of osteolysis-related diseases caused by excessive osteoclast formation and activity.<\/jats:p>","DOI":"10.3390\/ijms151221913","type":"journal-article","created":{"date-parts":[[2014,11,28]],"date-time":"2014-11-28T14:11:21Z","timestamp":1417183881000},"page":"21913-21934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["The Inhibition of RANKL-Induced Osteoclastogenesis through the Suppression of p38 Signaling Pathway by Naringenin and Attenuation of Titanium-Particle-Induced Osteolysis"],"prefix":"10.3390","volume":"15","author":[{"given":"Wengang","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanlong","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tian","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zanjing","family":"Zhai","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Qu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengxiao","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"},{"name":"Department of Orthopedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanqing","family":"Mao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Tang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Qin","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics,  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,  Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1016\/j.actbio.2014.02.003","article-title":"Contributions of human tissue analysis to understanding the mechanisms of loosening and osteolysis in total hip replacement","volume":"10","author":"Gallo","year":"2014","journal-title":"Acta Biomater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"780","DOI":"10.2106\/00004623-200704000-00012","article-title":"Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030","volume":"89","author":"Kurtz","year":"2007","journal-title":"J. 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