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

• Published in: Arthritis research & therapy 2008-01, Vol.10 (4), p.R87-R87, Article R87
• Main Authors: Heathfield, Sarah Kathleen, Le Maitre, Christine Lyn, Hoyland, Judith Alison
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aging, Premature - metabolism; Biomarkers - metabolism; Caveolin 1 - metabolism; Caveolins; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Degeneration (Pathology); Genetic aspects; Health aspects; Humans; Intervertebral Disc - metabolism; Intervertebral Disc - pathology; Intervertebral disk; Middle Aged; Physiological aspects; Risk factors; Spinal Diseases - etiology; Spinal Diseases - metabolism; Spinal Diseases - pathology; Stress, Physiological - physiology
• ISSN: 1478-6354; 1478-6362; 1478-6354
• DOI: 10.1186/ar2468

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. 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. 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. 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.