A Slowly Progressive and Reproducible Animal Model of Intervertebral Disc Degeneration Characterized by MRI, X-Ray, and Histology

Sobajima, Satoshi; Kompel, John; Kim, Joseph S.; Wallach, Corey J.; Robertson, Douglas D.; Vogt, Molly T.; Kang, James D.; Gilbertson, Lars G.

doi:10.1097/01.brs.0000148048.15348.9b

Cited by 244 publications

(281 citation statements)

References 21 publications

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“…This lack of mechanical consequence indicates that a 33-gauge needle may prove suitable for administering developmental therapies to the nucleus pulposus of rat intervertebral discs, whereas a larger gauge needle may create an altered mechanical environment and initiate degeneration. [40][41][42] Nucleus glycosaminoglycan content was linearly correlated with neutral zone properties, while the elastic stiffness at high magnitudes of both compression and tension were not dependent upon nucleus glycosaminoglycan content. Thus, glycosaminoglycan depletion results in a state of hypermobility at relatively low applied loads.…”

Section: Discussionmentioning

confidence: 93%

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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Section: Discussionmentioning

confidence: 93%

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

et al. 2006

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“…[13][14][15][16][17] It is generally believed that needle puncture injury with small-gauge needles is not expected to cause damage, whereas needle puncture injury with large-gauge needles leads to degenerative changes. AF needle puncture injury to the disc in rabbits using needles of different gauges has been demonstrated to result in slow progressive degeneration as measured using magnetic resonance imaging (MRI), radiograph, histology, and polymerase chain reaction.…”

mentioning

confidence: 99%

Needle Puncture Injury Affects Intervertebral Disc Mechanics and Biology in an Organ Culture Model

Korecki¹,

Costi²,

Iatridis³

2008

Spine

133

114

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Study Design-A bovine intervertebral disc organ culture model was used to study the effect of needle puncture injury on short-term disc mechanics and biology.Objective-To test the hypothesis that significant changes in intervertebral disc structure, mechanics, and cellular response would be present within 1 week of needle puncture injury with a large-gauge needle but not with a small-gauge needle.Summary of Background Data-Defects in anulus fibrosus induced by needle puncture injury can compromise mechanical integrity of the disc and lead to degeneration in animal models. The immediate and short-term mechanical and biologic response to anulus injury through needle puncture in a large animal model is not known.Methods-Bovine caudal intervertebral discs were harvested, punctured posterolaterally using 25G and 14G needles, and placed in organ culture for 6 days. Discs underwent a daily dynamic compression loading protocol for 5 days from 0.2 to 1 MPa at 1 Hz for 1 hour. Disc structure and function were assessed with measurements of dynamic modulus, creep, height loss, water content, proteoglycan loss to the culture medium, cell viability, and histology.Results-Needle puncture injury caused a rapid decrease in dynamic modulus and increase in creep during 1-hour loading, although no changes were detected in water content, disc height, or proteoglycan lost to the media. Cell viability was maintained except for localized cell death at the needle insertion site. An increase in cell number and possible remodeling response was seen in the insertion site in the nucleus pulposus.Conclusion-Relatively minor disruption in the disc from needle puncture injury had immediate and progressive mechanical and biologic consequences with important implications for the use of discography, and repair-regeneration techniques. Results also suggest diagnostic techniques sensitive to mechanical changes in the disc may be important for early detection of degenerative changes in response to anulus injury. Keywordsspine; intervertebral disc; organ culture; needle puncture; bovine; discography; mechanics; dynamic compression loading ©2008, Lippincott Williams & WilkinsAddress correspondence and reprint requests to James C. Iatridis, PhD, 201 Votey Building, 33 Colchester Avenue, Burlington, VT, 05405; E-mail: E-mail: james.iatridis@uvm.edu. NIH Public AccessAuthor Manuscript Spine (Phila Pa 1976 Current and future procedures for intervertebral disc (IVD) diagnosis, repair, and regeneration often require needle injection to the nucleus pulposus (NP) through the anulus fibrosus (AF). For example, discography, which requires injection of a radio opaque dye into the NP, has a best-case positive predictive value of 50% to 60%, and results in potential AF damage through needle puncture. 4 Intradiscal electrothermal treatment also requires puncture of the AF and additional anular disruption using a catheter. 5 Future treatments including growth factor therapy, 6 tissue engineering, 7 and gene and cell therapy 8,9 may also require puncture of t...

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“…Rat caudal discs are used in this study because of the substantial and growing body of in vivo and ex vivo mechanobiology research using small animals (e.g. rabbits, rats, and mice) (Iatridis et al, 1999;Gruber et al, 2002;Ching et al, 2003;Hsieh and Lotz, 2003;Norcross et al, 2003;Risbud et al, 2003;Maclean et al, 2004;An et al, 2005;Kim et al, 2005;Sobajima et al, 2005). It was recently reported that mouse lumbar discs matched the previously reported nonlinear response of human lumbar discs while mouse caudal discs only matched the linear response provided differences in cross-sectional areas were accounted for (Sarver and Elliott, 2005).…”

Section: Introductionmentioning

confidence: 66%

Role of endplates in contributing to compression behaviors of motion segments and intervertebral discs

MacLean

Owen

Iatridis

2007

Journal of Biomechanics

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The purpose of this study was to gain an improved understanding of the mechanical behavior of the intervertebral disc in the presence and absence of the vertebral endplates. Mechanical behaviors of rat caudal motion segments, vertebrae and isolated disc explants under two different permeability conditions were investigated and viscoelastic behaviors were evaluated using a stretched-exponential function to describe creep and recovery behaviors. The results demonstrated that both vertebrae and discs underwent significant deformations in the motion segment even under relatively low-loading conditions. Secondly, disruption of the collagenous network had minimal impact on equilibrium deformations of disc explants as compared to disc deformations occurring in the motion segments provided that vertebral deformations were accounted for; however, differences in endplate permeability conditions had a significant effect on viscoelastic behaviors. Creep occurred more quickly than recovery for motion segment and explant specimens. In addition, disc explants and motion segments both exhibited non-recoverable deformations under axial compression under lowand high-loading conditions. Results have important implications for interpreting the role of vertebral endplates in contributing to disc mechanical behaviors and direct application to mechanobiology studies involving external loading to rodent tail intervertebral discs.

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A Slowly Progressive and Reproducible Animal Model of Intervertebral Disc Degeneration Characterized by MRI, X-Ray, and Histology

Cited by 244 publications

References 21 publications

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

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

Needle Puncture Injury Affects Intervertebral Disc Mechanics and Biology in an Organ Culture Model

Role of endplates in contributing to compression behaviors of motion segments and intervertebral discs

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