Abstract
The spine is routinely subjected to repetitive complex loading consisting of axial compression, torsion, flexion and extension. Mechanical loading is one of the important causes of spinal diseases, including disc herniation and disc degeneration. It is known that static and dynamic compression can lead to progressive disc degeneration, but little is known about the mechanobiology of the disc subjected to combined dynamic compression and torsion. Therefore, the purpose of this study was to compare the mechanobiology of the intervertebral disc when subjected to combined dynamic compression and axial torsion or pure dynamic compression or axial torsion using organ culture. We applied four different loading modalities [1. control: no loading (NL), 2. cyclic compression (CC), 3. cyclic torsion (CT), and 4. combined cyclic compression and torsion (CCT)] on bovine caudal disc explants using our custom made dynamic loading bioreactor for disc organ culture. Loads were applied for 8 h/day and continued for 14 days, all at a physiological magnitude and frequency. Our results provided strong evidence that complex loading induced a stronger degree of disc degeneration compared to one degree of freedom loading. In the CCT group, less than 10% nucleus pulposus (NP) cells survived the 14 days of loading, while cell viabilities were maintained above 70% in the NP of all the other three groups and in the annulus fibrosus (AF) of all the groups. Gene expression analysis revealed a strong up-regulation in matrix genes and matrix remodeling genes in the AF of the CCT group. Cell apoptotic activity and glycosaminoglycan content were also quantified but there were no statistically significant differences found. Cell morphology in the NP of the CCT was changed, as shown by histological evaluation. Our results stress the importance of complex loading on the initiation and progression of disc degeneration.
Highlights
Healthy intervertebral disc (IVD) function as essential mechanical load-transmitters between the vertebrae, allowing compression, bending, flexion and torsion of the spine
There was a slight increase in mean disc height of around 3% in the no loading (NL) and cyclic torsion (CT) groups, while disc height was decreased by about 2% in the groups with cyclic compression (CC and cyclic compression and torsion (CCT))
Cell viability in the nucleus pulposus (NP) of the CCT group dropped to 10.99616.3%, which was significantly lower than the cell viability in the NP of all the other three groups and in the annulus fibrosus (AF) of all groups
Summary
Healthy intervertebral disc (IVD) function as essential mechanical load-transmitters between the vertebrae, allowing compression, bending, flexion and torsion of the spine. It is clear that some of the causes of low back pain, such as disc herniation and degeneration, are influenced by mechanical loading, which is related to the life style and daily activity of the individual [1,2,3]. The intervertebral disc experiences various complex loading conditions of different magnitudes and directions consisting of compression, axial rotation, flexion and extension. Epidemiological studies identified both compression and axial torsion as risk factors in the development of disc degeneration and back pain [4,5]. Characteristics of DD include increased cell death, a decrease in disc height due to a loss of essential matrix components which can be reflected by an increased matrix catabolic gene expression (MMP-3, MMP-13, ADAMTS-4) but decreased anabolic gene expression (collagens and proteoglycans), increased inflammatory response (TNF-a, IL-1b, IL-6) and changes of mechanical properties of the disc (increased stiffness) [8]
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