title: Methylglyoxal activates NF-κB nuclear translocation and induces COX-2 expression via a p38-dependent pathway in synovial cells.
abstract: OBJECTIVE
  There is growing evidence of an increased prevalence of osteoarthritis (OA) among people with diabetes. Synovial inflammation and increased expression of cyclooxygenase-2 (COX-2) are two key features of patients with OA. Methylglyoxal (MGO) is a common intermediate in the formation of advanced glycation end-products, and its concentration is also typically higher in diabetes. In this study, we investigated the effects of the treatment of different MGO concentrations to rabbit HIG-82 synovial cells on COX-2 expression.
  
  
  METHODS
  The MGO induced COX-2 mRNA expression was detected by quantitative polymerase chain reaction. The MGO induced COX-2 protein production and its signaling pathways were detected by western blotting. The nuclear factor-kappa B (NF-κB) nuclear translocation by MGO was examined by immunofluorescence.
  
  
  RESULTS
  In the present study, we find that MGO has no toxic effects on rabbit synovial cells under the experimental conditions. Our analysis demonstrates that MGO induced COX-2 mRNA and protein production. Moreover, MGO induces p38-dependent COX-2 protein expression as well as the phosphorylations of extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and Akt/mammalian target of rapamycin (mTOR)/p70S6K; however, inhibition of JNK and Akt/mTOR/p70S6K phosphorylations further activates COX-2 protein expression. Furthermore, MGO is shown to activate of nuclear factor-kappa B (NF-κB) nuclear translocation.
  
  
  CONCLUSIONS
  Our results suggest that MGO can induce COX-2 expression via a p38-dependent pathway and activate NF-κB nuclear translocation in synovial cells. These results provide insight into the pathogenesis of the synovial inflammation under the diabetic condition associated with higher MGO levels.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan; Department of Physical Medicine and Rehabilitation, Chung Shan Medical University, School of Medicine and Hospital, Taichung City, Taiwan.
authors.forename: Chuan-Chao
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Ophthalmology, Cardinal Tien Hospital, New Taipei City, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Chan
authors.affiliation: Medical Research Center, Cardinal Tien Hospital, New Taipei City, Taiwan.
authors.forename: Yi-Pin
authors.initials: YP
authors.lastname: Huang
authors.affiliation: Medical Research Center, Cardinal Tien Hospital, New Taipei City, Taiwan.
authors.forename: Shu-Hao
authors.initials: SH
authors.lastname: Hsu
authors.affiliation: Medical Research Center, Cardinal Tien Hospital, New Taipei City, Taiwan; Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei City, Taiwan.
authors.forename: Chuen-Lin
authors.initials: CL
authors.lastname: Huang
authors.affiliation: Department of Physical Medicine and Rehabilitation, Chung Shan Medical University, School of Medicine and Hospital, Taichung City, Taiwan. Electronic address: sujutsai@gmail.com.
authors.forename: Su-Ju
authors.initials: SJ
authors.lastname: Tsai
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000494:pharmacology*; D011817:Rabbits; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis*
chemical_list: D016328:NF-kappa B; D011765:Pyruvaldehyde; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Akt; Cyclooxygenase (COX)-2; Mammalian target of rapamycin (mTOR); Methylglyoxal (MGO); Mitogen-activated protein kinase (MAPK); Nuclear factor-kappa B (NF-κB); Synovial cells; p70S6K