In vivo remodeling of intervertebral discs in response to short‐ and long‐term dynamic compression

Abstract

This study evaluated how dynamic compression induced changes in gene expression, tissue composition, and structural properties of the intervertebral disc using a rat tail model. We hypothesized that daily exposure to dynamic compression for short durations would result in anabolic remodeling with increased matrix protein expression and proteoglycan content, and that increased daily load exposure time and experiment duration would retain these changes but also accumulate changes representative of mild degeneration. Sprague-Dawley rats (n ¼ 100) were instrumented with an Ilizarov-type device and divided into three dynamic compression (2 week-1.5 h/day, 2 week-8 h/day, 8 week-8 h/day at 1 MPa and 1 Hz) and two sham (2 week, 8 week) groups. Dynamic compression resulted in anabolic remodeling with increased matrix mRNA expression, minimal changes in catabolic genes or disc structure and stiffness, and increased glysosaminoglycans (GAG) content in the nucleus pulposus. Some accumulation of mild degeneration with 8 week-8 h included loss of annulus fibrosus GAG and disc height although 8-week shams also had loss of disc height, water content, and minor structural alterations. We conclude that dynamic compression is consistent with a notion of ''healthy'' loading that is able to maintain or promote matrix biosynthesis without substantially disrupting disc structural integrity. A slow accumulation of changes similar to human disc degeneration occurred when dynamic compression was applied for excessive durations, but this degenerative shift was mild when compared to static compression, bending, or other interventions that create greater structural disruption. Keywords: intervertebral disc; disc degeneration; mechanobiology; animal model; biomechanics Substantial socioeconomic problems that result from low back pain are often associated with intervertebral disc (IVD) degeneration.1 The etiology of disc degeneration is complex and multifactorial with heredity, mechanical loading, and nutrition all playing significant roles.2-7 These contributing factors are interactive and strongly affected by aging. For example, degradation of the molecular structure of the disc during aging can also render it more susceptible to mechanical injuries. 4 Loading type, magnitude, duration, and frequency all influence cell metabolic responses and matrix remodeling. 5,8,9 Mechanical loading may induce remodeling directly via tissue stresses that may predispose the matrix to damage or through alterations in the biosynthetic response due to mechanically altered biosynthesis of proteins and enzymes.8 IVD degeneration is manifested morphologically through a loss in disc height, decreased nucleus volume, and in a loss of distinction between nucleus pulposus (NP) and annulus fibrosus (AF). In more severe degeneration, a more extensive loss in IVD structural organization has been noted, with formation of clefts and tears in the AF.2 Degenerative changes on the biochemical level are noted first in the NP, with a loss of glysosaminoglycans (GA...

The effects of dynamic loading on the intervertebral disc

“…Wuertz et al [127] suggested that the disc responded anabolically to dynamic compression at a high daily exposure, such as 8 h/day instead of 1.5 h/day. For instance, a 2-week dynamic compression of 8 h/day at 1 MPa and 1 Hz caused up-regulation of anabolic gene expression in the NP of the rat tail.…”

“…In a study of IHP, Kasra et al [50] also reported a magnitude-dependent and frequency-dependent response of collagen synthesis in porcine AF and NP cells, respectively. Furthermore, a long duration of loading (8 h/ day) was beneficial for the NP, but was degenerative in the AF [127]. It is unclear why the duration of loading resulted in a different response in the NP and the AF; it could be due to the fundamental difference in the characteristic of the cell types or the matrix environment of the two compartments.…”

“…There is evidence that a spinal loading, which comprises the diurnal variation in IVD pressure from a low magnitude (around 0.2 MPa) to a high magnitude (around 0.6 MPa) dynamic loading at a physiological frequency (0.2-1 Hz), is essential to maintain the health and function of the non-pathological IVD. Dynamic loading of a certain magnitude, frequency and duration has been shown to maintain the matrix balance within the disc [70,71,122,127] and even provide a synergistic effect on the differentiation of stem cells towards the chondrocytic lineage under the influence of growth factors [14,21,40,41,48,54,66,83,90,112,113]. Conversely, prolonged exposure to hypo-or hyper-physiological loading can be harmful to the disc.…”

“…Conversely, prolonged exposure to hypo-or hyper-physiological loading can be harmful to the disc. In an unloaded condition, the IVD swells and starts to lose proteoglycans [118]; static loading causes cell death and induces disc degeneration [4,67,68,89,110]; a hyper-physiological magnitude and frequency of dynamic loading induces signs of disc degeneration [45,56,70,71,122,127]. A comprehensive review on the effect of hydrostatic pressure, osmotic pressure, tensile loading and static compression on the IVD has been reported by Setton and Chen [106].…”

Intervertebral disc changes with angulation, compression and reduced mobility simulating altered mechanical environment in scoliosis

“…The intention was to distinguish the relative effects of imposed angulation, compressive force and reduced mobility to the progressive wedging of intervertebral discs by imposing permutations of alterations in biomechanical conditions in different groups of animals. Rat tail discs were selected because the rat tail is easily accessible for controlled application of compression forces [3,10,17,26,31] and because of the rapid growth of these animals [26].…”