A Novel Rabbit Model of Mild, Reproducible Disc Degeneration by an Anulus Needle Puncture: Correlation Between the Degree of Disc Injury and Radiological and Histological Appearances of Disc Degeneration

Masuda, Koichi; Aota, Yoichi; Muehleman, Carol; Imai, Yoshiyuki; Okuma, M; Thonar, Eugene J-M.A.; Andersson, Gunnar; An, Howard S.

doi:10.1097/01.brs.0000148152.04401.20

Cited by 600 publications

(688 citation statements)

References 32 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: 90%

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: 90%

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

et al. 2006

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“…The 4‐µm‐thick sagittal sections were stained with safranin O–fast green or picrosirius red staining for morphological analysis. Histological grading of NP/AF in mouse L4/L5 IVD was performed following the system described by Masuda et al (2005), and degenerative changes in EP were graded according to a modification to the scoring system described by Boos et al (2002). Briefly, the grading system in the NP and AF evaluated four different parameters: NP cellularity, border between NP and AF, matrix of the NP, and lamellar morphology in the AF.…”

Section: Methodsmentioning

confidence: 99%

FOXO are required for intervertebral disk homeostasis during aging and their deficiency promotes disk degeneration

et al. 2018

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Intervertebral disk (IVD) degeneration is a prevalent age‐associated musculoskeletal disorder and a major cause of chronic low back pain. Aging is the main risk factor for the disease, but the molecular mechanisms regulating IVD homeostasis during aging are unknown. The aim of this study was to investigate the function of FOXO, a family of transcription factors linked to aging and longevity, in IVD aging and age‐related degeneration. Conditional deletion of all FOXO isoforms (FOXO1, 3, and 4) in IVD using the Col2a1Cre and AcanCreER mouse resulted in spontaneous development of IVD degeneration that was driven by severe cell loss in the nucleus pulposus (NP) and cartilaginous endplates (EP). Conditional deletion of individual FOXO in mature mice showed that FOXO1 and FOXO3 are the dominant isoforms and have redundant functions in promoting IVD homeostasis. Gene expression analyses indicated impaired autophagy and reduced antioxidant defenses in the NP of FOXO‐deficient IVD. In primary human NP cells, FOXO directly regulated autophagy and adaptation to hypoxia and promoted resistance to oxidative and inflammatory stress. Our findings demonstrate that FOXO are critical regulators of IVD homeostasis during aging and suggest that maintaining or restoring FOXO expression can be a therapeutic strategy to promote healthy IVD aging and delay the onset of IVD degeneration.

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“…This method has been used for monitoring changes in animal models of disc regeneration [63]. However, repeated X-rays for monitoring changes in disc height are not possible for assessing repair rates in humans and the sensitivity may be inadequate for the slow rate of repair in humans if only one or two time points can be imaged.…”

Section: How Do We Assess Success?mentioning

confidence: 99%

Tissue engineering and the intervertebral disc: the challenges

2008

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Disc degeneration is a common disorder. Although the back pain that can develop in association with this is rarely life-threatening, the annual cost in terms of morbidity, lost productivity, medical expenses and workers' compensation benefits is significant. Surgical intervention as practised currently is directed towards removing the damaged or altered tissue. Development of new treatment modalities is critical as there is a growing consensus that the strategies used currently for symptomatic degenerative disc disease may not be effective. Accordingly, there is a need to develop an entirely new way to treat this disorder; regenerative medicine and tissue engineering approaches appear particularly promising in this regard. This paper reviews some of the challenges that currently are limiting the clinical application of this approach to the treatment of disc degeneration.

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A Novel Rabbit Model of Mild, Reproducible Disc Degeneration by an Anulus Needle Puncture: Correlation Between the Degree of Disc Injury and Radiological and Histological Appearances of Disc Degeneration

Abstract: The needle puncture approach, using 16G to 21G needles, resulted in a reproducible decrease of disc height and magnetic resonance imaging grade. The ease of the procedure and transfer of the methodology will benefit researchers studying disc degeneration.

Cited by 600 publications

References 32 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

FOXO are required for intervertebral disk homeostasis during aging and their deficiency promotes disk degeneration

Tissue engineering and the intervertebral disc: the challenges

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