title: Therapeutic potential of the proteasome inhibitor Bortezomib on titanium particle-induced inflammation in a murine model.
abstract: Wear particle-induced aseptic loosening has been recognized as a harmful inflammatory process that jeopardizes the longevity of total joint replacement. The proteasome controls the activation of NF-κB and subsequent inflammatory mediators, such as TNF-α and IL-1β; thus, we investigated whether proteasome inhibition can ameliorate wear particle-induced inflammation in a murine model. A total of 48 BALB/C mice were divided into four groups. Titanium (Ti) particles were injected into the established air pouches of all mice (except negative controls) to provoke inflammation, and then 0.1 or 0.5 mg/kg of Bortezomib (Bzb, a proteasome inhibitor) was administered to ameliorate the inflammation response, while air pouches without Bzb administration were used as loading controls. The air pouches were harvested 2 or 7 days after Bzb injection for molecular and histological analyses. Inflammation responses in the air pouch tissues of Bzb treatment groups are lower than those in the Ti-stimulated group, and this occurs in a dose-dependent manner. Bzb can significantly attenuate the severity of Ti-induced inflammation in air pouches.
authors.affiliation: Department of Orthopedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University School of Medicine, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Mao
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Pan
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Xianlong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use; D000069286:Bortezomib; D005260:Female; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D007595:Joint Prosthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000096:biosynthesis; D010014:Osteolysis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011475:Prosthesis Failure; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D014025:Titanium / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001897:Boronic Acids; D018836:Inflammation Mediators; D016328:NF-kappa B; D061988:Proteasome Inhibitors; D011719:Pyrazines; D014409:Tumor Necrosis Factor-alpha; D000069286:Bortezomib; D014025:Titanium; D051550:I-kappa B Kinase