DNA methylation of SPARC and chronic low back pain

Molecular Pain

Laura S Stone⁴  Moshe Szyf⁵  Jean Ouellet²  Lisbet Haglund⁶  Kathleen M Anderson¹  Thomas Dashwood⁵  Magali Millecamps⁴  Sebastian Alvarado⁵  Maral Tajerian³ 

[1] Department of Physical Medicine & Rehabilitation, University of Minnesota Medical School, 420 Delaware Street S.E., Minneapolis, MN, 55454, USA;Division of Orthopaedic Surgery, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada;Department of Neurology and Neurosurgery, McGill University, Faculty of Medicine, 3801 University Street, Montreal, Quebec, H3A 2B4, Canada;Faculty of Dentistry, McGill University, 3640 University Street, Montreal, Quebec, H3A 2B2, Canada;Sackler Program for Epigenetics & Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal, Québec H3G 1Y6, Canada;Orthopaedics Research Laboratory, McGill University Health Centre, 687 Pine Avenue West, Montreal Quebec, H3A 1A1, Canada

关键词: disc degeneration;    gene expression;    aging;    intervertebral disc;    epigenetics;    DNA methylation;    back pain;    SPARC;   

Others  :  865793
DOI  :  10.1186/1744-8069-7-65

 received in 2011-06-20, accepted in 2011-08-25,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Tajerian et al; licensee BioMed Central Ltd.

【 图 表 】

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