Effects of TGF-ß1 and IL-1ß on expression of ADAMTS enzymes and TIMP-3 in human intervertebral disc degeneration.

The aim of this study was to investigate the effects of transforming growth factor-ß1 (TGF-ß1) and interleukin-1ß (IL-1ß) on the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzymes and their inhibitor, tissue inhibitor of metalloproteinase 3 (TIMP-3), in human intervertebral disc (IVD) degeneration. Cells from patients with IVD degeneration were cultured with Dulbecco's modified Eagle's medium with Ham's F12 nutrient mixture (DMEM/F12) medium at 37°C in a 5% CO2 incubator. Cell proliferation was measured by cell counting kit-8 assays with varying concentrations of TGF-ß1 and IL-1ß in a time-response experiment. The mRNA and protein expression levels of ADAMTS-4, ADAMTS-5 and TIMP-3 were detected with qPCR and western blot analysis, respectively. The present study demonstrated that TGF-ß1 promoted nucleus pulposus (NP) cell proliferation, decreased the expression of ADAMTS-4 and -5 and increased the expression of TIMP-3. By contrast, the IL-1ß treatment inhibited NP cell proliferation and significantly increased the expression of ADAMTS-4 and -5. However, IL-1ß appeared to have no marked effect on the expression of TIMP-3. This study suggests that TGF-ß1 and IL-1ß are involved in the synthesis and degradation of the extracellular matrix and may act as potential therapeutic targets for the prevention or reversal of IVD degeneration.