Effects of Degeneration on the Biphasic Material Properties of Human Nucleus Pulposus in Confined Compression

Johannessen, Wade; Elliott, Dawn M.

doi:10.1097/01.brs.0000192236.92867.15

Cited by 221 publications

(248 citation statements)

References 31 publications

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“…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.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 51%

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

Boxberger

Auerbach

Sen

et al. 2008

Spine

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Study Design-An in vivo model resembling early stage disc degeneration in the rat lumbar spine.Objective-Simulate the reduced glycosaminoglycan content and altered mechanics observed in intervertebral disc degeneration using a controlled injection of chondroitinase ABC (ChABC).Summary of Background Data-Nucleus glycosaminoglycan reduction occurs early during disc degeneration; however, mechanisms through which degeneration progresses from this state are unknown. Animal models simulating this condition are essential for understanding disease progression and for development of therapies aimed at early intervention.Methods-ChABC was injected into the nucleus pulposus, and discs were evaluated via micro-CT, mechanical testing, biochemical assays, and histology 4 and 12 weeks after injection.Results-At 4 weeks, reductions in nucleus glycosaminoglycan level by 43%, average height by 12%, neutral zone modulus by 40%, and increases in range of motion by 40%, and creep strain by 25% were found. Neutral zone modulus and range of motion were correlated with nucleus glycosaminoglycan. At 12 weeks, recovery of some mechanical function was detected as range of motion and creep returned to control levels; however, this was not attributed to glycosaminoglycan restoration, because mechanics were no longer correlated with glycosaminoglycan.Conclusion-An in vivo model simulating physiologic levels of glycosaminoglycan loss was created to aid in understanding the relationships between altered biochemistry, altered mechanics, and altered cellular function in degeneration.Keywords intervertebral disc; degeneration; nucleus pulposus; glycosaminoglycan; animal model; chondroitinase ABC Intervertebral disc degeneration is a complex progression of structural, biochemical, and biological alterations that contribute to compromised mechanical function and in some instances discogenic low back pain. Despite the prevalence of the condition, with billions of dollars in associated health care costs paid annually in the United States, 1 treatments for disc degeneration and the associated pain are limited, due in part to the lack of a thorough understanding of the mechanisms at play. Among the early degenerative changes is a NIH Public AccessAuthor Manuscript Spine (Phila Pa 1976). Author manuscript; available in PMC 2009 June 15. Published in final edited form as:Spine (Phila Pa 1976 breakdown of large aggregating proteoglycans reducing the sulfated glycosaminoglycan content in the nucleus pulposus. 2-4 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. 5-8 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 anima...

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Section: Nih-pa Author Manuscriptmentioning

confidence: 51%

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

Boxberger

Auerbach

Sen

et al. 2008

Spine

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“…As shown by Johannessen et al for the NP [34] and Iatridis et al [31,32] and Gu et al [27] for the AF, these changes affect the biomechanical behavior of the disc. Due to the reduction of the proteoglycan content in the NP, the swelling capacity of the NP tissue decreases significantly; at the same time, due to breakdown of collagen, the permeability of the tissue increases.…”

Section: Matrix Changesmentioning

confidence: 91%

“…Within the nucleus pulposus, the water content was found to decrease from 5.8 gH 2 O/g dry weight at an age of 14 years (85 % volume fraction) to 3.3 gH 2 O/g dry weight at age 91 years (75 %) [66]. For the NP, primarily, a loss of proteoglycans was observed [7,34]. For the AF, a change in water content, although to a more limited extent in comparison with the NP, as well as collagen content is observed during ageing [7].…”

Section: Cellular and Matrix Changesmentioning

confidence: 95%

Ageing and degenerative changes of the intervertebral disc and their impact on spinal flexibility

et al. 2014

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Purpose Degeneration of the intervertebral disc is associated with various morphological changes of the disc itself and of the adjacent structures, such as reduction of the water content, collapse of the intervertebral space, disruption and tears, and osteophytes. These morphological changes of the disc are linked to alterations of the spine flexibility. This paper aims to review the literature about the ageing and degenerative changes of the intervertebral disc and their link with alterations in spinal biomechanics, with emphasis on flexibility. Methods Narrative literature review. Results Clinical instability of the motion segment, usually related to increased flexibility and hypothesized to be connected to early, mild disc degeneration and believed to be responsible for low back pain, was tested in numerous in vitro studies. Despite some disagreement in the findings, a trend toward spinal stiffening with the increasing degeneration was observed in most studies. Tests about tears and fissures showed inconsistent results, as well as for disc collapse and dehydration. Vertebral osteophytes were found to be effective in stabilizing the spine in bending motions. Conclusions The literature suggests that the degenerative changes of the intervertebral disc and surrounding structures lead to subtle alteration of the mechanical properties of the functional spinal unit. A trend toward spinal stiffening with the increasing degeneration has been observed in most studies.

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“…At low applied loads, the nucleus pulposus likely resists load directly, and also, through the developed pressure, distributes the applied force radially to create a circumferential resistance in the annulus fibrosus. As glycosaminoglycan content of the nucleus is reduced, a decreased swelling pressure and increased aggregate modulus 16 lead to an altered load sharing between the nucleus and annulus, and larger deformations may occur prior to annulus fibers being engaged and loaded. 6,43,44 On the other hand, the nucleus plays less of a role at high compressive and tensile loads: the annulus fibrosus resists the applied loads and is dominant in determining deformation behavior via both the developed circumferential hoop tension and also direct axial support by the annulus glycosaminoglycan and water network.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11] Mechanical alterations due to degeneration have been noted within each tissue region of the disc as well as in the elastic and viscoelastic response of the entire bone-disc-bone motion segment. [12][13][14][15][16][17][18] However, the quantitative relationships between altered biochemistry and mechanics remain rather unclear, as it is difficult to isolate the multiple biochemical changes occurring in human degeneration.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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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

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Effects of Degeneration on the Biphasic Material Properties of Human Nucleus Pulposus in Confined Compression

Cited by 221 publications

References 31 publications

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

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

Ageing and degenerative changes of the intervertebral disc and their impact on spinal flexibility

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

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