Region Specific Response of Intervertebral Disc Cells to Complex Dynamic Loading: An Organ Culture Study Using a Dynamic Torsion-Compression Bioreactor

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.

Duration-dependent influence of dynamic torsion on the intervertebral disc: an intact disc organ culture study

“…This indicates that different loading imposes different effects on the disc cells, where 8 h of physiological dynamic compression is not harmful but dynamic torsion is. This finding also explains partially the results of the previous study, i.e., an extended period (8 h/day) of complex dynamic torsion-compression loading has caused a substantial cell death in the NP [7]. It was counter-intuitive to find that torsion was more harmful to the NP cells than AF cells.…”

TRPC6 in simulated microgravity of intervertebral disc cells

“…Although genetics plays an essential role in the onset of ageing and the progression of degeneration [3], mechanical loading and damage, particularly of the lumbar spine, have been identified as contributing factors [4]. Whereas physiological levels of mechanical stress support the metabolic balance of the IVD [5], hyper-physiological mechanical stresses or mechanical unloading biases the IVD towards catabolism, inflammation and reduced viability, hence promoting degeneration [6]. Mechanical unloading, occurring, e.g.…”

Transcriptional profiling distinguishes inner and outer annulus fibrosus from nucleus pulposus in the bovine intervertebral disc

“…Therefore, model organisms, such as the cow, are used for in vitro cellular and ex vivo biomechanical studies of the IVD [14,15]. The bovine tail IVD represents a good model for the non-degenerate human IVD: the bovine NP retains few notochordal cells and whole transcriptome analyses identified similar phenotypic marker genes as in humans [6,16,17].…”