The effect of metallic magnesium degradation products on osteoclast-induced osteolysis and attenuation of NF-κB and NFATc1 signaling

• Published in: Biomaterials 2014-08, Vol.35 (24), p.6299-6310
• Main Authors: Zhai, Zanjing, Qu, Xinhua, Li, Haowei, Yang, Ke, Wan, Peng, Tan, Lili, Ouyang, Zhengxiao, Liu, Xuqiang, Tian, Bo, Xiao, Fei, Wang, Wengang, Jiang, Chuan, Tang, Tingting, Fan, Qiming, Qin, An, Dai, Kerong
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Advanced Basic Science; Animals; Cell Death - drug effects; Cell Line; Cytokines - biosynthesis; Dentistry; Gene Expression Regulation - drug effects; Hydrogen-Ion Concentration - drug effects; Magnesium; Magnesium - pharmacology; Mice, Inbred C57BL; Models, Biological; NF-kappa B - metabolism; NF-κB; NFATC Transcription Factors - metabolism; NFATc1; Osteoclast; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteoclasts - pathology; Osteogenesis - drug effects; Osteogenesis - genetics; Osteolysis; Osteolysis - pathology; RANK Ligand - pharmacology; Signal Transduction - drug effects; Signal Transduction - genetics; Skull - drug effects; Skull - pathology; Time Factors
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2014.04.044

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.