Nucleus pulposus glycosaminoglycan content is correlated with axial mechanics in rat lumbar motion segments

Abstract

The unique biochemical composition and structure of the intervertebral disc allow it to support load, permit motion, and dissipate energy. With degeneration, both the biochemical composition and mechanical behavior of the disc are drastically altered, yet quantitative relationships between the biochemical changes and overall motion segment mechanics are lacking. The objective of this study was to determine the contribution of nucleus pulposus glycosaminoglycan content, which decreases with degeneration, to mechanical function of a rat lumbar spine motion segment in axial loading. Motion segments were treated with varying doses of Chondroitinase-ABC (to degrade glycosaminoglycans) and loaded in axial cyclic compression-tension, followed by compressive creep. Nucleus glycosaminoglycan content was significantly correlated ( p < 0.05) with neutral zone mechanical behavior, which occurs in low load transition between tension and compression (stiffness: r ¼ 0.59; displacement: r ¼ À0.59), and with creep behavior (viscous parameter h 1 : r ¼ 0.34; short time constant t 1 : r ¼ 0.46). These results indicate that moderate decreases in nucleus glycosaminoglycan content consistent with early human degeneration affect overall mechanical function of the disc. These decreases may expose the disc to altered internal stress and strain patterns, thus contributing through mechanical or biological mechanisms to the degenerative cascade. ß

The Effect of Nucleus Pulposus Crosslinking and Glycosaminoglycan Degradation on Disc Mechanical Function

“…We observed, in a paired comparison before and after the treatment, that a 33G needle (0.2 mm dia) leads to an acute mechanical change of approximately 20% in the neutral zone properties. It is notable, however, that more recent studies comparing the effect of needle stick to intact control in an unpaired t-test show no statistical difference and the average neutral zone mechanics were within 6% of each other (Boxberger et al 2005(Boxberger et al , 2006. Axial neutral zone mechanics depend upon the nucleus pulposus pressurization (Martinez et al 1997;Riches et al 2002;Johannessen et al 2004;Johannessen et al 2005) so, although we did not directly measure pressure, the needle puncture may have partially depressurized the nucleus pulposus in this study.…”

“…This may also be due to the concentration of ChABC used, as the effects of ChABC are concentration-dependent (Fry et al 1991;Sasaki et al 2001). Further studies looking into the effects of ChABC concentration on the GAG content and the mechanics are being conducted (Boxberger et al 2005(Boxberger et al , 2006.…”

An In Vivo Model of Reduced Nucleus Pulposus Glycosaminoglycan Content in the Rat Lumbar Intervertebral Disc

“…Specifically, studies have shown hypermobility at low loads 34 and altered viscoelastic properties including increased creep rate and deformation 35 in early degeneration, mechanical changes that are attributed to the reduction in nucleus glycosaminoglycan. 5,7,8,36 At 4 weeks postinjection, neutral zone modulus, range of motion, and creep were all altered in a manner consistent with the expected changes in a degenerating disc, and were altered to the same degree as observed after an equivalent ChABC injection in vitro. Further, both neutral zone modulus and range of motion were linearly correlated with nucleus glycosaminoglycan content 4 weeks postinjection-relationships that were identical to those determined in the absence of biologic activity.…”

“…[2][3][4] This reduction of glycosaminoglycan content has an impact on the mechanical function of the disc: the ability to imbibe and bind water is diminished, pressure within the nucleus is decreased, and ultimately, the mechanical function of the nucleus and the entire motion segment is altered. [5][6][7][8] It is plausible that progressive degeneration follows this reduced glycosaminoglycan content and altered mechanics, yet this ultimately remains a hypothesis, and knowledge of specific mechanisms and interactions is limited. To this end, in vivo animal models simulating the condition of decreased nucleus pulposus glycosaminoglycan content as observed in early degeneration would be of great utility.…”

Intervertebral Disc Degeneration and Low Back Pain: Molecular Mechanisms and Stem Cell Therapy

“…(72) The aggrecan molecules become degraded, with smaller fragments being able to leach from the tissue more readily than larger portions. (30) Decreasing aggrecan content in the NP leads to reduced hydration (73), leading in turn to impaired mechanical function (74,75). A less hydrated, more fibrous NP is unable to evenly distribute compressive forces between the vertebral bodies.…”