Caveolin-1 expression and stress-induced premature senescence in human intervertebral disc degeneration.
BACKGROUND
Chronic and debilitating low back pain is a common condition and a huge economic burden. Many cases are attributed to age-related degeneration of the intervertebral disc (IVD); however, age-related degeneration appears to occur at an accelerated rate in some individuals. We have previously demonstrated biomarkers of cellular senescence within the human IVD and suggested a role for senescence in IVD degeneration. Senescence occurs with ageing but can also occur prematurely in response to stress. We hypothesised that stress-induced premature senescence (SIPS) occurs within the IVD and here we have investigated the expression and production of caveolin-1, a protein that has been shown previously to be upregulated in SIPS.


METHODS
Caveolin-1 gene expression in human nucleus pulposus (NP) cells was assessed by conventional and quantitative real-time polymerase chain reaction (PCR), and caveolin-1 protein expression was examined within human IVDs using immunohistochemistry. The correlation between caveolin-1 and p16INK4a (biomarker of cellular senescence) gene expression was investigated using quantitative real-time PCR.


RESULTS
Caveolin-1 gene expression and protein expression were demonstrated within the human IVD for the first time. NP cells from degenerate discs exhibited elevated levels of caveolin-1 which did not relate to increasing chronological age. A negative correlation was observed between gene expression for caveolin-1 and donor age, and no correlation was found between caveolin-1 protein expression and age. A positive correlation was identified between gene expression of caveolin-1 and p16INK4a.


CONCLUSIONS
Our findings are consistent with a role for caveolin-1 in degenerative rather than age-induced changes in the NP. Its expression in IVD tissue and its association with the senescent phenotype suggest that caveolin-1 and SIPS may play a prominent role in the pathogenesis of IVD degeneration.
Heathfield
Sarah Kathleen
SK
Faculty of Medical and Human Sciences, Tissue Injury and Repair Group, Research School of Clinical and Laboratory Sciences, The University of Manchester, Manchester, UK.
Le Maitre
Christine Lyn
CL
Hoyland
Judith Alison
JA
D000328:Adult; D000368:Aged; D019588:Aging, Premature / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D013122:Spinal Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013312:Stress, Physiological / Q000502:physiology*
D015415:Biomarkers; D051242:Caveolin 1; D019941:Cyclin-Dependent Kinase Inhibitor p16