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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 4/2008

Open Access 01-08-2008 | Research article

Caveolin-1 expression and stress-induced premature senescence in human intervertebral disc degeneration

Authors: Sarah Kathleen Heathfield, Christine Lyn Le Maitre, Judith Alison Hoyland

Published in: Arthritis Research & Therapy | Issue 4/2008

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Abstract

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 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.

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.
Appendix
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Metadata
Title
Caveolin-1 expression and stress-induced premature senescence in human intervertebral disc degeneration
Authors
Sarah Kathleen Heathfield
Christine Lyn Le Maitre
Judith Alison Hoyland
Publication date
01-08-2008
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2008
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2468

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