title: The inhibition of RANKL-induced osteoclastogenesis through the suppression of p38 signaling pathway by naringenin and attenuation of titanium-particle-induced osteolysis.
abstract: 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-κB (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.
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. wwg1532@163.com.
authors.forename: Wengang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. challengewu1988@163.com.
authors.forename: Chuanlong
authors.initials: C
authors.lastname: Wu
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. poetian@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Tian
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. shliuxuqiang@163.com.
authors.forename: Xuqiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. eryijiuyuan@163.com.
authors.forename: Zanjing
authors.initials: Z
authors.lastname: Zhai
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. xinhua_qu@126.com.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Qu
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. jc720u@hotmail.com.
authors.forename: Chuan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. terryoy@126.com.
authors.forename: Zhengxiao
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. 13761360486@163.com.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. wzy1532@sina.com.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. dr.qinan@gmail.com.
authors.forename: An
authors.initials: A
authors.lastname: Qin
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. zhuzhenan2006@126.com.
authors.forename: Zhenan
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001862:Bone Resorption / Q000150:complications / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D010014:Osteolysis / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D053245:RANK Ligand / Q000494:pharmacology*; D014025:Titanium; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D044950:Flavanones; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; D000841:Anisomycin; D014025:Titanium; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C005273:naringenin