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c-Jun N-terminal kinase and nuclear factor κB mediate nitric oxide-induced expression of matrix metalloproteinase-13

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Abstract

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.

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Acknowledgements

This work was supported by Beijing Institute of Tropical Diseases. We are grateful to Bing-qiang Wang, Gao-Chao Zhao, Shu-lei Zhao, and Zhe Xu, PhD for assistance.

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Correspondence to Ai Guo or Jun-Chao Gu.

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Yang, L., Guo, A. & Gu, JC. c-Jun N-terminal kinase and nuclear factor κB mediate nitric oxide-induced expression of matrix metalloproteinase-13. International Orthopaedics (SICOT) 35, 1261–1266 (2011). https://doi.org/10.1007/s00264-010-1056-y

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