title: DNA methylation of SPARC and chronic low back pain.
abstract: BACKGROUND
  The extracellular matrix protein SPARC (Secreted Protein, Acidic, Rich in Cysteine) has been linked to degeneration of the intervertebral discs and chronic low back pain (LBP). In humans, SPARC protein expression is decreased as a function of age and disc degeneration. In mice, inactivation of the SPARC gene results in the development of accelerated age-dependent disc degeneration concurrent with age-dependent behavioral signs of chronic LBP.DNA methylation is the covalent modification of DNA by addition of methyl moieties to cytosines in DNA. DNA methylation plays an important role in programming of gene expression, including in the dynamic regulation of changes in gene expression in response to aging and environmental signals. We tested the hypothesis that DNA methylation down-regulates SPARC expression in chronic LBP in pre-clinical models and in patients with chronic LBP.
  
  
  RESULTS
  Our data shows that aging mice develop anatomical and behavioral signs of disc degeneration and back pain, decreased SPARC expression and increased methylation of the SPARC promoter. In parallel, we show that human subjects with back pain exhibit signs of disc degeneration and increased methylation of the SPARC promoter. Methylation of either the human or mouse SPARC promoter silences its activity in transient transfection assays.
  
  
  CONCLUSIONS
  This study provides the first evidence that DNA methylation of a single gene plays a role in chronic pain in humans and animal models. This has important implications for understanding the mechanisms involved in chronic pain and for pain therapy.
authors.affiliation: Alan Edwards Centre for Research on Pain, McGill University, 740 Dr, Penfield Avenue, Montreal, Quebec, H3A 1A4, Canada.
authors.forename: Maral
authors.initials: M
authors.lastname: Tajerian
authors.forename: Sebastian
authors.initials: S
authors.lastname: Alvarado
authors.forename: Magali
authors.initials: M
authors.lastname: Millecamps
authors.forename: Thomas
authors.initials: T
authors.lastname: Dashwood
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Anderson
authors.forename: Lisbet
authors.initials: L
authors.lastname: Haglund
authors.forename: Jean
authors.initials: J
authors.lastname: Ouellet
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
authors.forename: Laura S
authors.initials: LS
authors.lastname: Stone
mesh_terms: D000328:Adult; D000375:Aging / Q000187:drug effects / Q000235:genetics; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D059350:Chronic Pain / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000150:complications / Q000235:genetics / Q000473:pathology; D017116:Low Back Pain / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015676:Osteonectin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D015676:Osteonectin; D001374:Azacitidine