Abstract: ObjectiveMechanical stress plays an important role in intervertebral disc degeneration which is closely related with low back pain. The effects of mechanical stress on disc degeneration and the mechanisms involved are poorly understood. In the present study, we investigated how different magnitudes of mechanical stretch affected human intervertebral disc cells. MethodsCells were subjected to 0%, 6%, 12%, or 18% elongation for 24 h using a Flexercell Strain Unit, and the mRNA expressions of anabolic genes (collagen-1A1, collagen-2A1, aggrecan, versican) and catabolic genes (MMP-3, MMP-13, ADAMTS-4, ADAMTS-5) were examined. ResultsThe results showed that the expression of collagen-1A1, collagen-2A1 and aggrecan, but not versican, were increased at 12%, and decreased at 18%, whereas catabolic genes: MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5, were increased at 18%. Interestingly, mechanical stretch induced a magnitude-dependent increase in ADAMTS-4 synthesis. Furthermore, the effect seems to be finely tuned by stretching-triggered activation of distinct mitogen-activated protein kinase cascades. Specifically, an ERK1/2specific inhibitor, U0126, significantly inhibited stretching-induced ADAMTS-4 expression, whereas the inhibitors of p38 and JNK, SP6000125 and SB203580 only slightly decreased stretching-induced ADAMTS-4 expression. ConclusionThese results indicate that different magnitudes of mechanical stretch influence the biological behavior of intervertebral disc cells, which profoundly affects intervertebral disc degeneration.

Key words: Mechanical stress, Intervertebral disc cells, ADAMTS-4, ERK