title: Therapeutic effects of p75 tumor necrosis factor receptor monoclonal antibody on a rat model of traumatic arthritis.
abstract: BACKGROUND
  The aim of the present study was to investigate the therapeutic effects of p75 tumor necrosis factor receptor monoclonal antibody D8F2 on a traumatic arthritis model in rats, and to explore the underlying mechanism.
  
  
  METHODS
  Forty male Sprague Dawley rats were randomly divided into five groups: (A) sham operation control group, (B) traumatic arthritis model group, (C) low-dose D8F2 group (1 mg/kg), (D) medium-dose D8F2 group (3 mg/kg), and (E) high-dose D8F2 group (10 mg/kg). Joint fluid samples were collected at 72 h after surgery, and enzyme-linked immunosorbent assay was performed to measure the following inflammatory factors: tumor necrosis factor α (TNF-α) and interleukin 1β. One week after the surgery, rats were killed, and immunohistochemical staining was applied to detect the matrix metalloproteinase (MMP1 and MMP3) expression in the synovium. In cultured synovial fibroblast experiments, the D8F2-induced ubiquitination of TNF receptor-associated factor 2 (TRAF2) was examined by immunoprecipitation, and nuclear translocation of p65 nuclear factor-κB (p65NF-κB) mediated by TNF-α and D8F2 was analyzed by western blotting.
  
  
  RESULTS
  In the traumatic arthritis model group, the inflammatory factors and MMPs were significantly increased relative to the sham operation control group (P < 0.05), whereas D8F2 could downregulate these factors in a dose-dependent manner (P < 0.05). The results from in vitro studies indicated that D8F2 can induce TRAF2 ubiquitination and inhibit the nuclear translocation of p65NF-κB mediated by TNF-α.
  
  
  CONCLUSIONS
  p75 Tumor necrosis factor receptor monoclonal antibody has a therapeutic effect on traumatic arthritis, which may occur via the downregulation of inflammatory factors and MMPs at the transcription level because of TRAF2 degradation and inhibited activation of NF-κB.
authors.affiliation: First-aid Center, Shanghai Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.
authors.forename: Yi Xin
authors.initials: YX
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.forename: Wen Li
authors.initials: WL
authors.lastname: Su
authors.forename: Qing
authors.initials: Q
authors.lastname: You
authors.forename: Zhi Qian
authors.initials: ZQ
authors.lastname: Hu
authors.forename: Zhi Guo
authors.initials: ZG
authors.lastname: Wang
authors.forename: Wen Xian
authors.initials: WX
authors.lastname: Zhu
authors.forename: Can Ping
authors.initials: CP
authors.lastname: Ruan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D007596:Joints / Q000293:injuries*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000037:antagonists & inhibitors* / Q000502:physiology; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D016328:NF-kappa B; D047889:Receptors, Tumor Necrosis Factor, Type II; D047992:TNF Receptor-Associated Factor 2; D020781:Matrix Metalloproteinase 1
keywords: Inflammatory factors; Matrix metalloproteinase; NF-κB; TRAF2; Traumatic arthritis; p75TNFR monoclonal antibody