Dysregulated expression of antioxidant enzymes in polyethylene particle-induced periprosthetic inflammation and osteolysis

• Published in: PloS one Vol. 13; no. 8; p. e0202501
• Main Authors: Peng, Kuo-Ti, Tsai, Meng-Hsueh, Lee, Chiang-Wen, Chiang, Yao-Chang, Chen, Pei-Chun, Chen, Chun-Chieh, Chang, Chih-Hsiang, Shih, Hsin-Nung, Chang, Pey-Jium
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.08.2018; Public Library of Science (PLoS)
• Subjects: Animals; Antioxidants; Artificial joints; Biocompatibility; Bioindicators; Biology and Life Sciences; Biomedical materials; Blood plasma; Bone surgery; Bone-Implant Interface; Care and treatment; Complications and side effects; Dose-response effects; Drug dosages; Enzymes; Exercise; Gene expression; Glutathione Peroxidase - metabolism; Hip replacement arthroplasty; Hospitals; IL-1β; Implantation; Implants, Experimental - adverse effects; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Inflammation - pathology; Interleukin-1beta - metabolism; Joint diseases; Knee; Knee replacement arthroplasty; Male; Malondialdehyde; Malondialdehyde - metabolism; Markers; Medicine and Health Sciences; NF-kappa B - metabolism; NF-κB protein; Orthopedics; Osteoclasts - metabolism; Osteoclasts - pathology; Osteolysis; Osteolysis - chemically induced; Osteolysis - metabolism; Osteolysis - pathology; Oxidative Stress; Particle Size; Particulate matter; Particulates; Physical activity; Polyethylene; Polyethylene - adverse effects; Polyethylenes; Prostheses; Proteins; RANK Ligand - metabolism; Rats; Rats, Wistar; Superoxide dismutase; Superoxide Dismutase - metabolism; Surgery; Surgical implants; TRANCE protein; Wear particles; United States > US; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0202501

Small wear particles (0.1-10 μm) in total joint replacement are generally considered as the major causative agent leading to periprosthetic inflammation and osteolysis. However, little is known about the roles of larger wear particles (10-100 μm) in periprosthetic inflammation and osteolysis. Additionally, although ample studies demonstrated that increased oxidative stress is critically involved in particle-induced inflammation and osteolysis, detailed changes in antioxidant enzymes expression in the disease development remain largely unclear. Herein, we used a rat knee prosthesis model to assess effects of polyethylene (PE) particles (20-60 μm) on the levels of oxidative stress markers such as malondialdehyde (MDA) and total antioxidant capacity (TAC) in blood plasma, and on the expression profiles of antioxidant enzymes in knee joint tissues. In combination with a forced-exercise intervention for all surgical rats, we found that the rat groups treated with both artificial joint and PE particles exhibited higher MDA levels and lower TAC levels, together with lower levels of physical activity and higher levels of inflammatory markers, than the sham group and the groups receiving artificial joint or PE particles alone at weeks 20-24 post-operatively. Dose-response relationships between the exposure to PE particles and the induction of oxidative stress and inflammation were also observed in the artificial joint/PE groups. Under such conditions, we unexpectedly found that most of antioxidant enzymes displayed pronounced up-regulation, with concomitant induction of inflammatory and osteoclast-inducing factors (including IL-1β, NF-κB and RANKL), in the artificial joint/PE groups as compared to the sham, artificial joint only, or PE only group. Only a few antioxidant enzymes including SOD2 and GPx2 showed down-regulation. Collectively, our findings demonstrate that implantation of artificial joint along with large PE particles synergistically trigger the induction of oxidative stress; however, down-regulation of many antioxidant enzymes may not necessarily occur during the disease development.