Senescence in human intervertebral discs.
Intervertebral discs demonstrate degenerative changes relatively early in life. Disc degeneration, in turn, is associated with back pain and disc herniation, both of which cause considerable clinical problems in the western world. Cell senescence has been linked to degenerative diseases of other connective tissues such as osteoarthritis. Thus we investigated the degree of cell senescence in different regions of discs from patients with different disc disorders. Discs were obtained from 25 patients with disc herniations; from 27 patients undergoing anterior surgery for either back pain due to degenerative disc disease (n = 25) or spondylolisthesis (n = 2) and from six patients with scoliosis. In addition, four discs were obtained post-mortem. Samples were classified as annulus fibrosus or nucleus pulposus and tissue sections were assessed for the degree of cell senescence (using the marker senescence-associated-beta-galactosidase (SA-beta-Gal)) and the number of cells present in clusters. There were significantly more SA-beta-Gal positive cells in herniated discs (8.5% of cells) than those with degenerative disc disease, spondylolisthesis, scoliosis, or cadaveric discs (0.5% of cells; P < 0.001). There was more senescence of cells of the nucleus pulposus compared to those of the annulus fibrosus and in herniated discs a higher proportion of cells in cell clusters (defined as groups of three or more cells) were SA-beta-Gal positive (25.5%) compared to cells not in clusters (4.2%, P < 0.0001). This study demonstrates an increased degree of cell senescence in herniated discs, particularly in the nucleus where cell clusters occur. These clusters have been shown previously to form via cell proliferation, which is likely to explain the increased senescence. These findings could have two important clinical implications: firstly, that since senescent cells are known to behave abnormally in other locations, they may lead to deleterious effects on the disc matrix and so contribute to the pathogenesis and secondly, cells from such tissue may not be ideal for cell therapy and repair via tissue engineering.
Roberts
S
S
Centre for Spinal Studies, Robert Jones and Agnes Hunt Orthopaedic and District Hospital, NHS Trust, Oswestry, Shropshire, SY10 7AG, UK. Sally.Roberts@rjah.nhs.uk
Evans
E H
EH
Kletsas
D
D
Jaffray
D C
DC
Eisenstein
S M
SM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology*; D002648:Child; D051445:Fibrocartilage / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology*; D007405:Intervertebral Disc Displacement / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D001616:beta-Galactosidase / Q000378:metabolism
D015415:Biomarkers; D001616:beta-Galactosidase