title: Caveolin-1 expression and stress-induced premature senescence in human intervertebral disc degeneration.
abstract: 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.
authors.affiliation: Faculty of Medical and Human Sciences, Tissue Injury and Repair Group, Research School of Clinical and Laboratory Sciences, The University of Manchester, Manchester, UK.
authors.forename: Sarah Kathleen
authors.initials: SK
authors.lastname: Heathfield
authors.forename: Christine Lyn
authors.initials: CL
authors.lastname: Le Maitre
authors.forename: Judith Alison
authors.initials: JA
authors.lastname: Hoyland
mesh_terms: 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*
chemical_list: D015415:Biomarkers; D051242:Caveolin 1; D019941:Cyclin-Dependent Kinase Inhibitor p16