intervertebral disc degeneration, model

Mechanobiology Research

Low back pain is a huge burden on our limited resources with limited knowledge of its pathophysiology. It is widely known that intervertebral disc degeneration (IDD) is intimately related, with the degree of degeneration associated with the severity of low back pain. The characteristics of intervertebral disc degeneration include disc height loss, proteoglycan loss, loss of water, annular fissures, and end plate calcification.

The degenerative process of the intervertebral disc has been seen as a phenotype change within the cells. This anabolic to catabolic shift seems to occur to the cells deep within the disc. One branch of research that studies the influence of mechanical forces on the biology is called Mechanobiology. In other words, can physical stressors on discs influence the process of degeneration? Can moving the disc is a certain way change the outcome of degeneration?



The Study

In this open access study, researchers were the first to investigate this kind of cyclical mechanical tension on the nucleus pulposus cell’s changing behaviour.  They extracted disc cells from caudal spines of (3-month-old) male Sprague-Dawley rats and conducted the mechanical testing using a device after the cells were cultured and prepared. They used this device to apply mechanical force on the cells of the nucleus pulposus (the centre of the disc) to see how the cells behaved under specific loading conditions.

Disc cell senescence involves telomere shortening,  free radical stress, DNA breakdown and cytokine proliferation. Mechanical loading conditions in the upright posture have been found to promote disc cell changes towards intervertebral disc degeneration in rats.  Studying the role of mechanical stress and the influence on disc health will benefit our understanding of disc pathogenesis. 

The results of this study showed a direct relationship of prolonged mechanical cyclic stress towards the catabolic shift of the cells in the nucleus pulposus. They concluded that unphysiological mechanical stress could push a disc into the degenerative cascade. They believe that eventually, too much mechanical stress can influence a cell’s behaviour and suggested that research continue searching the optimal mechanical environment for intervertebral disc cells.

At Dynamic Disc Designs, we work to bring dynamic models to the practitioner to help in the discussions related to motion and the spine.

 



Diurnal Disc Shape

The spine undergoes natural shape and fluid changes over the course of 24 hours. Often, back pain symptoms vary as well over the day and night cycle.  But the small changes and the links to pain have not been researched thoroughly. Here, a group of researchers from Duke University looked at the reliability of measuring intervertebral disc shape with recumbent MRI. This large avascular structure is linked to back pain and has significant diurnal variation in the human body. It would seem wise to further understand its diurnal disc shape changes.

Some people feel pain in the mornings and others feel things more so at the end of the day. Yet others feel pain more so when they lie down.

The intervertebral disc hydraulically keeps vertebrae separated. Water is squeezed out throughout the day as the human frame is vertical, and this water gets resorbed when an individual lays down. During the process, the disc changes shape and height. And when pain is involved, these shape and height changes can bear increased ( or decreased ) physical stress on structures that may be inflammatory. These can include annular fissures, disc bulges, disc herniations, disc protrusions, encroaching nerve or rootlets of nerves and the shingling of facet joints, just to name a few.

The purpose of this study was to determine intra and inter-rater reliability using MRI to measure diurnal changes of the intervertebral discs.

They did find excellent reliability, and interestingly they saw the most significant change in the posterior annulus region of L5-1. The diurnal variations were in line with what others had seen in previous work. Boos at al. in 1996 saw a 1-2mm change over the course of an 8h workday while Hutton et al. in 2003 saw a volume change of 1-2 cm3.

This research is essential if we are to fully understand back pain origins. Often pain syndromes related to the lower back present with symptoms that are diurnal. At Dynamic Disc Designs, we have models to help explain these subtle but significant changes to the discs, assisting patients to understand the onset of their pains and the diurnal disc shape and the natural variations.

 

Dynamic, Disc , Modeling, Research

Dynamic Loading of the Intervertebral Disc – Ex vivo culturing and what can we learn?

For decades, the study of the intervertebral disc and the process that leads to degeneration has kept researchers very busy. This quest to fully understand the mechanisms that lead to water loss and proteoglycan content of the nucleus pulposus seems to be in the forebrain of spine investigators in hopes that it will provide clues on how to reverse the degenerative process…or at least prevent it.

Degenerative discs are arguably the most common cause of low back pain 1 with the cost affecting millions of people worldwide 2. The intervertebral disc plays a crucial role in the maintenence of bony vertebral spacing in the spine to allow movement. And when it starts to fail, it compromises the biomechanics. So, the search for regenerative strategies continues and hence the reason for this write-up.

One of the foregoing approaches to studying ways to rebuild human discs is to culture them outside of the body which is called ex vivo (outside life) research. In a recent publication in European Cells and Materials 3 these researchers were able to maintain cell life by loading the disc in a dynamic way. The branch of science that looks at how forces can influence real living tissues is called mechanobiology.

By stimulating the discs with motion, the cells remained alive for 14 days without any blood supply. Interestingly, the cells died when too much force was used whereas using medium cyclic forces maintained their viability. You can read the full text here.

This kind of research is VERY important in the greater understanding of how to keep the most important structure in the spine happy and viable. It also leads the way in revealing how much force is optimal (and the timing of it) for a healthy spine.

 

  1. Adams MA, Lama P, Zehra U, Dolan P (2015) Why do some intervertebral discs degenerate, when others (in the same spine) do not? Clin Anat 28: 195-204.
  2.  Katz JN (2006) Lumbar disc disorders and low-back pain: Socioeconomic factors and consequences. J Bone Joint Surg Am 88 Suppl 2: 21-24.
  3.  European Cells and Materials Vol. 31 2016 (pages 26-39).
regeneration - degenerated disc

Will there be regeneration of degenerated discs?

For decades a degenerated disc was thought to be a slow descent towards spinal dysfunction. However, when searching out terms like “degeneration” in PubMed, for example, the word “regeneration” is starting to show up in the searches along side degeneration.

Recently, at the Engineering in Medicine and Biology Society, 2004. IEMBS ’04. 26th Annual International Conference of the IEEE , Lotz et al. presented a paper (Mechanobiology in Intervertebral Disc Degeneration and Regeneration) explaining that while viewing the disc cells in-vivo they observed a temporal and spatial relationship to disc loading and the potential to influence their behaviour. They stated that by studying these load influences, it could lead to understand disc health and tolerance injury states.

“Our data demonstrates that these cells respond differently to pressure and distortion and survive in the discs mechanical/loading environment…intriguingly setting the stage for disc repair”

Mechanobiology is the study of how mechanics influences biology. Why does exercise help and why does sitting in a chair, without movement, often makes thing worse? Understanding the mechanics will give us insights on how we can influence cells to kick start anabolic behaviour and repair.

In 2004, Setton described  “Information on the mechanisms that govern cell responses to mechanical stimuli in the intervertebral disc are just emerging” in Cell Mechanics and Mechanobiology in the Intervertebral Disc . Back pain is the leading cause of disability wordwide and the second most common cause of physician visits. Therefore it only makes sense to look carefully at the influence of mechanics on the intervertebral disc cells. 

So, the future does look promising…especially when we are learning that the inflow fluid dynamics are greater than the outflow across the endplate.

At Dynamic Disc Designs Corp. we like to stay abreast of the literature, and highlight it, especially when it comes to mechanobiological strategies that can potentially regenerate degenerated discs.