Interleukin-1 inhibits Sox9 and collagen type Ⅱ expression via nuclear factor-κB in the cultured human intervertebral disc cells
摘要Background The most significant biological change in intervertebral disc degeneration is the decrease of chondrocyte specific gene and protein expression of Sox9 and collagen type Ⅱ. Interleukin-1 (IL-1) is not expressed in the normal intervertebral disc tissue but increases in the degenerated intervertebral disc tissue. This suggests that IL-1 may play a role in regulation of the expression of Sox9 and collagen type Ⅱ.Methods Human intervertebral disc cells were isolated and cultured. Sox9 and collagen type Ⅱ expression during treatment with IL-1, with or without the nuclear factor-κB (NF-κB) activity inhibitor curcumin, were detected by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, and the activity of the NF-κB signaling pathway was detected by the electrophoretic mobility shift assay (EMSA).Results IL-1 lowered the mRNA level and protein expression of Sox9 and collagen type Ⅱ in the cultured intervertebral disc cells in a dose dependent manner (P <0.05), and this effect was attenuated by curcumin. Curcumin alone had no effect on Sox9 and collagen type Ⅱ expression (P >0.05). IL-1 at concentrations of 0.1 ng/ml, 1 ng/ml and 10 ng/ml could stimulate the activity of NF-κB in the intervertebral disc cells in a dose dependent manner (P <0.05) that was inhibited by curcumin.Conclusions We demonstrated the previously unknown function of IL-1 in inhibiting Sox9 and collagen type II via NF-κB in the intervertebral disc cells. This inhibition can be attenuated by curcumin, which is an effective NF-κB activity inhibitor.
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