PMID- 24011916 OWN - NLM STAT- MEDLINE DCOM- 20140207 LR - 20131209 IS - 1095-8673 (Electronic) IS - 0022-4804 (Linking) VI - 186 IP - 1 DP - 2014 Jan TI - Therapeutic effects of p75 tumor necrosis factor receptor monoclonal antibody on a rat model of traumatic arthritis. PG - 234-9 LID - S0022-4804(13)00720-8 [pii] LID - 10.1016/j.jss.2013.07.047 [doi] AB - 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 alpha (TNF-alpha) and interleukin 1beta. 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-kappaB (p65NF-kappaB) mediated by TNF-alpha 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-kappaB mediated by TNF-alpha. 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-kappaB. CI - Crown Copyright (c) 2014. Published by Elsevier Inc. All rights reserved. FAU - Wang, Yi Xin AU - Wang YX AD - First-aid Center, Shanghai Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China. FAU - Xu, Kai AU - Xu K FAU - Su, Wen Li AU - Su WL FAU - You, Qing AU - You Q FAU - Hu, Zhi Qian AU - Hu ZQ FAU - Wang, Zhi Guo AU - Wang ZG FAU - Zhu, Wen Xian AU - Zhu WX FAU - Ruan, Can Ping AU - Ruan CP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130820 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (Antibodies, Monoclonal) RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 0 (Receptors, Tumor Necrosis Factor, Type II) RN - 0 (TNF Receptor-Associated Factor 2) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Animals MH - Antibodies, Monoclonal/*therapeutic use MH - Arthritis/*drug therapy MH - Cytokines/analysis MH - Disease Models, Animal MH - Joints/*injuries MH - Male MH - Matrix Metalloproteinase 1/analysis MH - NF-kappa B/antagonists & inhibitors MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Tumor Necrosis Factor, Type II/*antagonists & inhibitors/physiology MH - TNF Receptor-Associated Factor 2/metabolism OTO - NOTNLM OT - Inflammatory factors OT - Matrix metalloproteinase OT - NF-kappaB OT - TRAF2 OT - Traumatic arthritis OT - p75TNFR monoclonal antibody EDAT- 2013/09/10 06:00 MHDA- 2014/02/08 06:00 CRDT- 2013/09/10 06:00 PHST- 2013/05/01 00:00 [received] PHST- 2013/07/16 00:00 [revised] PHST- 2013/07/24 00:00 [accepted] PHST- 2013/09/10 06:00 [entrez] PHST- 2013/09/10 06:00 [pubmed] PHST- 2014/02/08 06:00 [medline] AID - S0022-4804(13)00720-8 [pii] AID - 10.1016/j.jss.2013.07.047 [doi] PST - ppublish SO - J Surg Res. 2014 Jan;186(1):234-9. doi: 10.1016/j.jss.2013.07.047. Epub 2013 Aug 20.