Abstract
Low back pain is a common ailment that affects millions of individuals each year and is linked to degeneration of the intervertebral discs in the spine. Intervertebral disc degeneration is known to result from an imbalance in anabolic and catabolic activity by disc cells. Due to the avascular nature of the intervertebral disc, oxygen deficiency may occur in the central nucleus pulposus (NP). The resulting hypoxia affects matrix regulation and energy metabolism of disc cells, although the mechanisms are not fully understood. This study investigates in vitro glucose consumption and gene expression by NP cells over time under varying oxygen tensions. Notochordal porcine NP cells were cultured in agarose discs at 21, 5, or 1% oxygen tension for 1, 5, or 10 days. The expression of 10 key matrix genes, as well as Brachyury (T), by NP cells was analyzed using RT-PCR. Glucose consumption was measured using a two-point method. Results show that culture time and oxygen tension significantly affect glucose consumption rates by porcine NP cells. There were also significant changes in T expression based on oxygen level and culture time. The 1% oxygen tension had a significantly higher T expression on day 10 than the other two groups, which may indicate a better maintenance of the notochordal phenotype. MMP 1 and 13 expression increased over time for all groups, while only the 5% group showed an increase over time for MMP 3. TIMP expression followed the direction of MMPs but to a lesser magnitude. Five percent and twenty-one percent oxygen tensions led to decreases in anabolic gene expression while 1% led to increases. Oxygen concentration and culture time significantly impacted glucose consumption rate and the gene expression of matrix regulatory genes with hypoxic conditions most accurately maintaining the proper NP phenotype. This information is valuable not only for understanding disc pathophysiology, but also for harnessing the potential of notochordal NP cells in therapeutic applications.
Highlights
Lower back pain causes an enormous socioeconomic burden in many developed nations due to high direct and indirect costs (Deyo et al, 1991; Waddell, 1996; Maetzel and Li, 2002; Katz, 2006)
The glucose consumption rate (GCR) showed a significant decline between days 1 and 10 for the 5% (p = 0.024) and 21% (p = 0.0004) oxygen tension groups
The overall goal of this study was to investigate the effects of oxygen tension levels and culture time on the activity and metabolism of notochordal nucleus pulposus (NP) cells
Summary
Lower back pain causes an enormous socioeconomic burden in many developed nations due to high direct and indirect costs (Deyo et al, 1991; Waddell, 1996; Maetzel and Li, 2002; Katz, 2006). Degenerative disc disease (DDD) of the intervertebral discs (IVD) of the spine is thought to be a major component in many cases of lower back pain, the exact mechanisms of this degeneration are poorly understood (Urban and Roberts, 2003). Disc degeneration is believed to be the result of improper matrix production by IVD cells, in which there is an imbalance in anabolic and catabolic activities (Adams and Roughley, 2006; Adams et al, 2009). With many potential contributing factors, elucidating which ones, or combinations thereof, initiate degeneration is an important task in order to better understand the pathways and mechanisms of DDD, and pose new treatment and/or regeneration modalities
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