Background and Aims: Low back pain has been attributed to degeneration of the intervertebral disc (IVD). Increased evidence of senescence biomarkers, including the protein caveolin-1, during IVD degeneration has been demonstrated and linked with disease development rather than ageing per se, suggesting that a particular type of senescence, stress-induced premature senescence (SIPS), occurs in disc degeneration. SIPS can be induced by cytokines such as interleukin-1 (IL-1 Since IL-1 is known to be an important mediator of the catabolic events in IVD degeneration we sought to investigate whether IL-1 induces expression of the senescence biomarker caveolin-1 in IVD cells and whether its induction is associated with markers of cell senescence.

Methods: Human nucleus pulposus (NP) cells cultured in monolayer were treated for 24 hours with 10ng/ml IL-1 Quantitative real-time RT-PCR was used to assess gene expression for caveolin-1 and cell cycle inhibitors p53, p21 and p16INK4a. Cells were stained for senescence-associated-galactosidase and flow cytometry performed to analyse cell cycle position.

Results: IL-1 treatment induced transcription of caveolin-1 at 8 hours after the start of treatment. This coincided with increased expression of the cell cycle inhibitors p21 and p16INK4a expression at 2 hours and p21 and p53 at 8 hours. Flow cytometry revealed that IL-1 treatment caused a shift away from the S phase of the cell cycle and treated cells exhibited senescence-associated-galactosidase staining.

Conclusion: Our findings indicate that IL-1 induces caveolin expression and features of cellular senescence in human NP cells suggesting a role for IL-1 and caveolin-1 in SIPS within the human IVD.

Conflicts of Interest: None

Source of Funding: Furlong Research Charitable Foundation