Journal
LIFE SCIENCES
Volume 149, Issue -, Pages 25-33Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2016.02.060
Keywords
Methylglyoxal (MGO); Nuclear factor-kappa B (NF-kappa B); Cyclooxygenase (COX)-2; Mitogen-activated protein kinase (MAPK); Akt; Mammalian target of rapamycin (mTOR); p70S6K; Synovial cells
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Aims: 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. Main 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-kappa B) nuclear translocation by MGO was examined by immunofluorescence. Key findings: 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-kappa B) nuclear translocation. Significance: Our results suggest that MGO can induce COX-2 expression via a p38-dependent pathway and activate NF-kappa B 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. (C) 2016 Elsevier Inc. All rights reserved.
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