title: The role of oxidative stress in aseptic loosening of total hip arthroplasties.
abstract: This study investigated the hypothesis that wear particle-induced oxidative stress initiates osteolysis after total hip arthroplasty (THA). Patient radiographs were scored for osteolysis and periprosthetic tissues were immunostained and imaged to quantify polyethylene wear, inflammation, and five osteoinflammatory and oxidative stress-responsive factors. These included high mobility group protein-B1 (HMGB1), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), 4-hydroxynonenal (4-HNE), and nitrotyrosine (NT). The results show wear debris correlated with inflammation, 4-HNE, NT and HMGB1, whereas inflammation only correlated with NT and HMGB1. Similar to wear debris and inflammation, osteolysis correlated with HMGB1. Additionally, osteolysis correlated with COX2 and 4-HNE, but not iNOS or NT. Understanding the involvement of oxidative stress in wear-induced osteolysis will help identify diagnostic biomarkers and therapeutic targets to prevent osteolysis after THA.
authors.affiliation: School of Biomedical Engineering, Science & Health Systems, Drexel University, Philadelphia, Pennsylvania; Department of Orthopaedic Surgery,Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Steinbeck
authors.affiliation: School of Biomedical Engineering, Science & Health Systems, Drexel University, Philadelphia, Pennsylvania.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Jablonowski
authors.affiliation: Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania; Rothman Institute at Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Javad
authors.initials: J
authors.lastname: Parvizi
authors.affiliation: Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Freeman
mesh_terms: D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects* / Q000295:instrumentation; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010014:Osteolysis / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D018384:Oxidative Stress; D011475:Prosthesis Failure; D011859:Radiography
chemical_list: D015415:Biomarkers
keywords: 4-hydroxynonenal (4-HNE); cyclooxygenase-2 (COX2); high mobility group protein-B1 (HMGB1); inducible nitric oxide synthase (iNOS); nitrotyrosine (NT); osteolysis