Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People's Republic of China.
Int Orthop. 2011 Aug;35(8):1261-6. doi: 10.1007/s00264-010-1056-y. Epub 2010 Jun 4.
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.
本研究旨在探讨一氧化氮（NO）诱导基质金属蛋白酶-13（MMP-13）表达的机制。通过 NO 供体（MAHMA-NONOate）刺激人软骨细胞（HCs），然后通过 Western blot 分析检测细胞丝裂原激活蛋白激酶（MAPKs）和核因子 κB（NF-κB）的激活以及 MMP-13 的表达。此外，还使用 MAPKs 和 NF-κB 的抑制剂研究了 NO 的细胞内信号转导。NO 诱导的 MMP-13 表达不受细胞外信号调节激酶（ERK）抑制剂（PD98059）或 p38 激酶抑制剂（SB203580）的抑制，但被 c-jun 末端激酶（JNK）抑制剂（SP600125）和 NF-κB 抑制剂（SN-50）抑制。此外，SP600125 处理可降低 NF-κB 激活，但 SN-50 处理对 JNK 激活没有明显影响。这些结果表明，NO 通过 HCs 中的 JNK 和 NF-κB 激活诱导 MMP-13 表达。
