HDAC Regulates Interleukin1?-induced ADAMTS-5 Expression Through MAPK Pathway In Articular Cartilage Cells

Objective:To observe interleukin1?-induced ADAMTS-5 expression in articulate cartilage cells and to investigate the regulatory mechanisms, and regulations of HDAC in this pathological progression. Methods:The rat articulate cartilage cells were treated with interleukin1? at different concentrations for 24 h. Total RNA was extracted and the ADAMTS-5 expression was examined by real-time PCR, cell viability was evaluated by CCK8. Cells were treated with interleukin1? at 10ng/mL at different time. Total protein and RNA was extracted and the ADAMTS-5 expression was examined by real-time PCR, MAPK signals were evaluated by western blotting. RT-PCR was performed to investigate the ADAMTS-5 mRNA expression of cells treated with different activators or inhibitors of MAPK. Different HDACs in cells from interleukin1?-treated and blank control was compared by real-time PCR. The effect and mechanism of suppression of HDAC inhibitor trichostatin A(TSA) and PCI-34051 in interleukin1?-induced ADAMTS-5 mRNA expression were showed by real-time PCR and western blotting, separately. Then siRNAs were used to repeat the inhibitors for verification. ResultsThe ADAMTS-5 expression of ACCs treated at different concentrations of interleukin1? was increased. CCK8 result suggests that interleukin1? has no inhibitory effect on viability of ACCs. The phosphorylation of ERK and JNK can be observed clearly at 15min?30min after treated by interleukin1?, and P38 not. ERK and JNK activators upregulate the ADAMTS-5 expression in cells, and inhibitors block the interleukin1?-induced ADAMTS-5 expression. HDAC4 and 8 showed a significant elevation in cells treated by interleukin1?, the HDAC inhibitor TSA and PCI-34051 could suppress interleukin1?-depended ADAMTS-5 expression. Interleukin1?-induced phosphorylation of ERK and JNK was weakened byTSA and PCI-34051. Knockdown of HDAC4 and HDAC8 by siRNA showed similar result in cartilage cells. Conclusion:Interleukin1? upregulate HDAC4 and HDAC8 in articular cartilage cells, in turn abundant ADAMTS-5 was secreted and extracellular matrix breakdown by switch the phosphorylation of ERK and JNK. The results of this stydy suggested that HDAC4 and HDAC8 could be novel therapeutic role for osteoarthritis.