The cell biology of intervertebral disc aging and degeneration.
Intervertebral disc degeneration, which mimics disc aging but occurs at an accelerated rate, is considered to be related to neck or low back pain and disc herniation. Degenerated discs show breakdown of the extracellular matrix and thus fail to bear the daily loadings exerted on the spine. Rather than a passive process of wear and tear, disc degeneration is an aberrant, cell-mediated response to progressive structural failure due to aging and other environmental factors such as abnormal mechanical stress. With aging and degeneration, disc cells undergo substantially biologic changes, including alternation of cell type in the nucleus pulposus, increased cell density but decreased number of viable cells as a result of increased cell death and increased cell proliferation, increased cell senescence, and altered cell phenotype which is characterized by compromised capability of synthesizing correct matrix components and by enhanced catabolic metabolism. These changes are involved in the process of disc degeneration through the complicated interactions among them. To retard or reverse disc degeneration, the abnormal conditions of the decreased viable cell population and the altered cell phenotype should be corrected. As potential therapies for disc degeneration, intradiscal protein injection, gene transfer and cell implantation are being understudied in vivo. Suppression of excessive apoptosis and accelerated senescence of disc cells may be other choices for treating disc degeneration. When performing a biologic therapy in order to repair or regenerate the degenerated disc, nutrient and biomechanical factors should also be incorporated, because they are the major causes of the biologic changes experienced by disc cells. Moreover, a very early intervention is indicated by the finding that the onset of human disc degeneration occurs as early as by adolescence.
Zhao
Chang-Qing
CQ
Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, 200092 Shanghai, China.
Wang
Li-Min
LM
Jiang
Lei-Sheng
LS
Dai
Li-Yang
LY
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D016923:Cell Death / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D051445:Fibrocartilage / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007405:Intervertebral Disc Displacement / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D013314:Stress, Mechanical