HEATHFIELD, S. K., LE MAITRE, C. L. and HOYLAND, J. A. (2008). Caveolin-1 expression and stress-induced premature senescence in human intervertebral disc degeneration. Arthritis research & therapy, 10 (4), R87.Full text not available from this repository.
Introduction: 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 p16(INK4a) (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 p16(INK4a). Conclusion: 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.
|Research Institute, Centre or Group:||Biomedical Research Centre|
|Depositing User:||Sarah Ward|
|Date Deposited:||22 Jun 2010 16:32|
|Last Modified:||22 Jun 2010 16:32|
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