title: Autophagy mediated CoCrMo particle-induced peri-implant osteolysis by promoting osteoblast apoptosis.
abstract: Wear particle-induced osteolysis is the leading cause of aseptic loosening, which is the most common reason for THA (total hip arthroplasty) failure and revision surgery. Although existing studies suggest that osteoblast apoptosis induced by wear debris is involved in aseptic loosening, the underlying mechanism linking wear particles to osteoblast apoptosis remains almost totally unknown. In the present study, we investigated the effect of autophagy on osteoblast apoptosis induced by CoCrMo metal particles (CoPs) in vitro and in a calvarial resorption animal model. Our study demonstrated that CoPs stimulated autophagy in osteoblasts and PIO (particle-induced osteolysis) animal models. Both autophagy inhibitor 3-MA (3-methyladenine) and siRNA of Atg5 could dramatically reduce CoPs-induced apoptosis in osteoblasts. Further, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Moreover, 3-MA also prevented osteoblast apoptosis in an antiautophagic way when tested in PIO model. Collectively, these results suggest that autophagy plays a key role in CoPs-induced osteolysis and that targeting autophagy-related pathways may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis.
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Zhenheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Naicheng
authors.initials: N
authors.lastname: Liu
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Gan
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Tongguo
authors.initials: T
authors.lastname: Shi
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Wang
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.
authors.forename: Nirong
authors.initials: N
authors.lastname: Bao
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Chen
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhao
authors.affiliation: a Jinling Hospital; Department of Orthopaedics; State Key Laboratory of Pharmaceutical Biotechnology; Nanjing University ; Nanjing , China.|b School of Medicine and School of Life Science; Nanjing University ; Nanjing , China.|c Jiangsu Provincial Laboratory for Nano-Technology; Nanjing University , Nanjing , China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010010:Osteoclasts / Q000166:cytology*; D010014:Osteolysis / Q000378:metabolism*
chemical_list: C025946:3-methyladenine; D000225:Adenine
keywords: aseptic loosening; autophagy; osteoblasts; osteolysis; wear particles