title: Effects of a proteasome inhibitor on the NF-κB signalling pathway in experimental osteoarthritis.
abstract: OBJECTIVE
  To evaluate the effects of the proteasome inhibitor MG-132 on the expression of nuclear factor (NF)-κB p65, inhibitor (I)-κB, tumour necrosis factor (TNF)-α, and interleukin (IL)-1β in the cartilage and synovial tissues of rats with osteoarthritis (OA), and to investigate the role that the ubiquitin/proteasome system (UPS) plays in the OA process.
  
  
  METHODS
  A total of 144 adult male Sprague Dawley rats were randomly assigned to four groups: anterior cruciate ligament transaction (ACLT) + MG-132 (ACLT/M), ACLT + dimethylsulfoxide (ACLT/D), sham surgery (Sham), and naïve + MG-132 (naïve/M). Pathological morphology was undertaken. mRNA expression levels of NF-κB p65, I-κB, TNF-α, and IL-1β were determined using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The activities of the 20S proteasome chymotrypsin-like and peptidylglutamyl-peptide hydrolase-like enzymes were measured using fluorospectrophotometry.
  
  
  RESULTS
  The Mankin scores at all time points in ACLT/M rats were significantly lower than those in ACLT/D rats (p < 0.05). Despite the NF-κB p65 in the synovial tissue at 2 weeks after surgery and IL-1β in the cartilage tissue at 12 weeks after surgery, mRNA expression levels of NF-κB p65, IL-1β, and TNF-α at other time points in ACLT/M were significantly lower than those in ACLT/D (p < 0.05). mRNA levels of I-κB in the cartilage tissue in ACLT/M were significantly higher than those in ACLT/D at 2 weeks after surgery (p < 0.05). mRNA levels of I-κB in the synovial tissue in ACLT/M were higher than those in ACLT/D at all time points, and the difference was significant at 4 weeks after surgery (p < 0.05). MG-132 decreased the activities of the 20S proteasome chymotrypsin-like and peptidylglutamyl-peptide hydrolase-like enzymes in the cartilage and synovial tissues of rats.
  
  
  CONCLUSIONS
  The proteasome inhibitor MG-132 delays the progress of OA by alleviating synovial inflammation and protecting the articular cartilage tissue.
authors.affiliation: Xiaoshan Traditional Chinese Medical Hospital , Zhengjiang Province , China.
authors.forename: R
authors.initials: R
authors.lastname: Quan
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.forename: Z
authors.initials: Z
authors.lastname: Yue
authors.forename: D
authors.initials: D
authors.lastname: Xin
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.forename: L
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002918:Chymotrypsin / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010805:Physical Conditioning, Animal; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D015853:Cysteine Proteinase Inhibitors; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D007976:Leupeptins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D010450:Endopeptidases; D002918:Chymotrypsin; D046988:Proteasome Endopeptidase Complex; C114177:peptidylglutamylpeptide hydrolase; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde