Effects of prostaglandin E2 on matrix metalloproteinase-2 activity in synovial cells and its signaling pathway

Abstract:

Objective：To investigate the effects of prostaglandin E2（PGE2） on matrix metalloproteinase-2（MMP-2） activity in syn－ovial cells and its signaling pathway so as to help discuss the possible effect of PGE2 on the healing ability of anterior cruciate liga－ment（ACL） after injury. Methods：Cultured synovial cells were treated with different concentrations of PGE2，and gelatin zymography assay was performed to detect MMP-2 activity at 12，24，48 h and 72 h after treatment.In presence of 10 ng/ml PGE2，each of seven signal pathway-specific inhibitors was respectively used to treat the synovial cells and MMP-2 activity was detected and semi-quan－tified. Results：PGE2 significantly elevated MMP-2 activity in synovial cells in a dose and time dependent manner. Inhibition of the p38 pathway with SB203850，ERK pathway with PD98059，and PKA pathway with KT5720 had no specific effect on PGE2-induced MMP-2 activity. However，inhibition of the JNK pathway with SP600125，AP-1 pathway with Curcumin，and nuclear factor-κB（NF-κB） pathway with Bay11-7082 and-7085 dramatically decreased PGE2-induced MMP-2 activity to 43%，25%，16% and 11%，respec－tively（P<0.01）. Conclusions：PGE2-induced MMP-2 activity in synovial cells may account for ACL’s poor healing ability after in－jury and this process might be regulated via JNK，AP-1 and NF-κB pathway. Inhibition of NF-κB pathway has the strongest decreas－ing effect on PGE2-induced MMP-2 activity，which provides a novel strategy for ACL repair.