The effect of metallic magnesium degradation products on osteoclast-induced osteolysis and attenuation of NF-κB and NFATc1 signaling |
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Authors: | Zanjing Zhai Xinhua Qu Haowei Li Ke Yang Peng Wan Lili Tan Zhengxiao Ouyang Xuqiang Liu Bo Tian Fei Xiao Wengang Wang Chuan Jiang Tingting Tang Qiming Fan An Qin Kerong Dai |
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Institution: | 1. 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;2. Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, People''s Republic of China;3. 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;4. Engineering Research Center of Digital Medicine and Clinical Translation, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200011, People''s Republic of China |
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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. |
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Keywords: | Magnesium Osteoclast Osteolysis NF-κB NFATc1 |
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