c-Jun N-terminal kinase and nuclear factor κB mediate nitric oxide-induced expression of matrix metalloproteinase-13.
The purpose of this study was to investigate the mechanism of expression of matrix metalloproteinase-13 (MMP-13) induced by nitric oxide (NO). Human chondrocytes (HCs) were stimulated with a NO donor (MAHMA-NONOate), then mitogen-activated protein kinases' (MAPKs) and nuclear factor κB' (NF-κB) activations and MMP-13' expression were assayed by Western blot analysis. Additionally, the intracellular signalling of NO was investigated using the inhibitors of MAPKs and NF-κB. NO-induced MMP-13 expression was not suppressed by extracellular signal-regulated kinase (ERK) inhibitor (PD98059) or inhibitors of p38 kinase (SB203580), but was inhibited by a c-jun terminal kinase (JNK) inhibitor (SP600125) and inhibitors of NF-κB (SN-50). Additionally, SP600125 treatment reduced NF-κB activation, but SN-50 treatment did not significantly affect JNK activation. These results suggest that NO induces MMP-13 expression by JNK and NF-κB activation in HCs.
Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People's Republic of China.
Lin
L
Yang
Ai
A
Guo
Jun-Chao
JC
Gu
D015153:Blotting, Western; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D004790:Enzyme Induction / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*
C105785:1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl; D004791:Enzyme Inhibitors; D006834:Hydrazines; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13