title: The effect of metallic magnesium degradation products on osteoclast-induced osteolysis and attenuation of NF-κB and NFATc1 signaling.
abstract: Wear particle-induced aseptic prosthetic loosening is one of the most common reasons for total joint arthroplasty (TJA). Extensive bone destruction (osteolysis) by osteoclasts plays an important role in wear particle-induced peri-implant loosening. Thus, strategies for inhibiting osteoclast function may have therapeutic benefit for prosthetic loosening. Here, we mimicked the process of magnesium (Mg) degradation in vivo and obtained Mg leach liquor (MLL) by immersing pure Mg in culture medium. For the first time, we demonstrated that MLL suppresses osteoclast formation, polarization, and osteoclast bone resorption in vitro. An in vivo assay demonstrated that MLL attenuates wear particle-induced osteolysis. Furthermore, we found that MLL significantly inhibits nuclear factor-κB (NF-κB) activation by retarding inhibitor-κB degradation and subsequent NF-κB nuclear translocation. We also found that MLL attenuates the expression of NFATc1 at both the protein and mRNA levels. These results demonstrate that MLL has anti-osteoclast activity in vitro and prevents wear particle-induced osteolysis in vivo. Collectively, our study suggests that metallic magnesium, one of the orthopedic implants with superior properties, has significant potential for the treatment of osteolysis-related diseases caused by excessive osteoclast formation and function.
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, 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 200011, 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 200011, People's Republic of China.
authors.forename: Haowei
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wan
authors.affiliation: Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Tan
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People's Republic of China; Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, People's Republic of China.
authors.forename: Zhengxiao
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, 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 200011, 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 200011, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, 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 200011, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, 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 200011, 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 200011, 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 200011, People's Republic of China; Engineering Research Center of Digital Medicine and Clinical Translation, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200011, People's Republic of China. Electronic address: krdai@163.com.
authors.forename: Kerong
authors.initials: K
authors.lastname: Dai
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010014:Osteolysis / Q000473:pathology*; D053245:RANK Ligand / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D012886:Skull / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
chemical_list: D000199:Actins; D016207:Cytokines; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; D008274:Magnesium
keywords: Magnesium; NF-κB; NFATc1; Osteoclast; Osteolysis