title: Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model.
abstract: Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure.
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Zanjing
authors.initials: Z
authors.lastname: Zhai
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Xuqiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Haowei
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China; Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, PR China.
authors.forename: Zhengxiao
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tang
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China. Electronic address: dr.qinan@gmail.com.
authors.forename: An
authors.initials: A
authors.lastname: Qin
authors.affiliation: Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China; Engineering Research Center of Digital Medicine and Clinical Translation, Ministry of Education of PR China, PR China; School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China. Electronic address: dongyungu@gmail.com.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Gu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D047348:Hydrolyzable Tannins / Q000494:pharmacology* / Q000627:therapeutic use; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis; D010014:Osteolysis / Q000188:drug therapy* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D012886:Skull / Q000166:cytology / Q000378:metabolism; D014025:Titanium / Q000494:pharmacology
chemical_list: D000199:Actins; D005960:Glucosides; D047348:Hydrolyzable Tannins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C024603:Geraniin; D014025:Titanium
keywords: ERK; Geraniin; NF-κB; Osteoclastogenesis; Osteolysis