Interleukin-1 inhibits Sox9 and collagen type II expression via nuclear factor-kappaB in the cultured human intervertebral disc cells.

Abstract

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-kappaB (NF-kappaB) activity inhibitor curcumin, were detected by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, and the activity of the NF-kappaB 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-kappaB 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-kappaB in the intervertebral disc cells. This inhibition can be attenuated by curcumin, which is an effective NF-kappaB activity inhibitor.