title: Myricetin prevents titanium particle-induced osteolysis in vivo and inhibits RANKL-induced osteoclastogenesis in vitro.
abstract: Titanium (Ti) particle-induced periprosthetic osteolysis and subsequent aseptic loosening are a primary reason for total hip arthroplasty failure. The aim of this study was to assess the effect of myricetin on Ti particle-induced osteolysis and osteoclastogenesis. We demonstrated that myricetin, a natural plant extract, exerts potent inhibitory effects on Ti particle-induced osteolysis in a mouse calvarial model. Further histological analysis indicated that the inhibition of osteoclast formation and function, and the secretion of inflammatory factors, are key targets for therapeutic agents in the treatment of wear particle-induced osteolysis. In vitro, we found that myricetin suppressed receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner. Moreover, myricetin significantly reduced the expression of osteoclast-specific markers in mouse bone marrow-derived macrophages, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, the calcitonin receptor, V-ATPase d2, c-fos, and nuclear factor of activated T cells (NFAT) c1. Further investigation revealed that myricetin inhibited osteoclastogenesis through the suppression of the nuclear factor-κB (NF-κB) signaling pathway and mitogen-activated protein kinase (MAPK) pathways involving extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase 1/2 (JNK1/2). While, the inhibition of TNF-α and IL-1β secretion was another reason for the suppressive effect of myricetin on Ti particle-induced osteolysis. Collectively, these findings suggest that myricetin is a potential natural agent for the treatment of periprosthetic osteolysis and other osteoclast-related osteolytic diseases.
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
authors.forename: Chuanlong
authors.initials: C
authors.lastname: Wu
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
authors.forename: Wengang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tian
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
authors.forename: Xuqiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Qu
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
authors.forename: Zanjing
authors.initials: Z
authors.lastname: Zhai
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
authors.forename: Haowei
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China. Electronic address: dr.qinan@gmail.com.
authors.forename: An
authors.initials: A
authors.lastname: Qin
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China. Electronic address: zhuzhenan2006@126.com.
authors.forename: Zhenan
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D010014:Osteolysis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D010316:Particle Size; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011897:Random Allocation; D014025:Titanium / Q000633:toxicity*
chemical_list: D005419:Flavonoids; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C040015:myricetin; D014025:Titanium
keywords: MAPK signaling; NF-κB signaling; Osteoclast formation; Osteoclastic bone resorption; Periprosthetic osteolysis