Correction to: ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

The author "Ashish D. Diwan" receives educational consultant fees from Nuvasive Inc.

ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

PURPOSE: To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model. METHODS: Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically. RESULTS: In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group. CONCLUSION: GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

Vulnerability of the superficial zone of immature articular cartilage to compressive injury.

OBJECTIVE: The zonal composition and functioning of adult articular cartilage causes depth-dependent responses to compressive injury. In immature cartilage, shear and compressive moduli as well as collagen and sulfated glycosaminoglycan (sGAG) content also vary with depth. However, there is little understanding of the depth-dependent damage caused by injury. Since injury to immature knee joints most often causes articular cartilage lesions, this study was undertaken to characterize the zonal dependence of biomechanical, biochemical, and matrix-associated changes caused by compressive injury. METHODS: Disks from the superficial and deeper zones of bovine calves were biomechanically characterized. Injury to the disks was achieved by applying a final strain of 50% compression at 100%/second, followed by biomechanical recharacterization. Tissue compaction upon injury as well as sGAG density, sGAG loss, and biosynthesis were measured. Collagen fiber orientation and matrix damage were assessed using histology, diffraction-enhanced x-ray imaging, and texture analysis. RESULTS: Injured superficial zone disks showed surface disruption, tissue compaction by 20.3 ± 4.3% (mean ± SEM), and immediate biomechanical impairment that was revealed by a mean ± SEM decrease in dynamic stiffness to 7.1 ± 3.3% of the value before injury and equilibrium moduli that were below the level of detection. Tissue areas that appeared intact on histology showed clear textural alterations. Injured deeper zone disks showed collagen crimping but remained undamaged and biomechanically intact. Superficial zone disks did not lose sGAG immediately after injury, but lost 17.8 ± 1.4% of sGAG after 48 hours; deeper zone disks lost only 2.8 ± 0.3% of sGAG content. Biomechanical impairment was associated primarily with structural damage. CONCLUSION: The soft superficial zone of immature cartilage is vulnerable to compressive injury, causing superficial matrix disruption, extensive compaction, and textural alteration, which results in immediate loss of biomechanical function. In conjunction with delayed superficial sGAG loss, these changes may predispose the articular surface to further softening and tissue damage, thus increasing the risk of development of secondary osteoarthritis.

Development of a standardized histopathology scoring system for intervertebral disc degeneration and regeneration in rabbit models-An initiative of the ORSspine section.

BACKGROUND: The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre-clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models. AIMS: The purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model. MATERIALS AND METHODS: The scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra-class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors. RESULTS: The final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus. DISCUSSION: Overall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field. CONCLUSION: This study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing.

Relationship between knee and ankle degeneration in a population of organ donors.

BACKGROUND: Osteoarthritis (OA) is a progressive degenerative condition of synovial joints in response to both internal and external factors. The relationship of OA in one joint of an extremity to another joint within the same extremity, or between extremities, has been a topic of interest in reference to the etiology and/or progression of the disease. METHODS: The prevalence of articular cartilage lesions and osteophytes, characteristic of OA, was evaluated through visual inspection and grading in 1060 adult knee/tali pairs from 545 cadaveric joint donors. RESULTS: Joint degeneration increased more rapidly with age for the knee joint, and significantly more knee joints displayed more severe degeneration than ankle joints from as early as the third decade. Women displayed more severe knee degeneration than did men. Severe ankle degeneration did not exist in the absence of severe knee degeneration. The effect of weight on joint degeneration was joint-specific whereby weight had a significantly greater effect on the knee. Ankle grades increasingly did not match within a donor as the grade of degeneration in either the left or the right knee increased. CONCLUSIONS: Gender and body type have a greater effect on knee joint integrity as compared to the ankle, suggesting that knees are more prone to internal causative effects of degeneration. We hypothesize that the greater variability in joint health between joints within an individual as disease progresses from normal to early signs of degeneration may be a result of mismatched limb kinetics, which in turn might lead to joint disease progression.

In-laboratory diffraction-enhanced X-ray imaging for articular cartilage.

The loss of articular cartilage characteristic of osteoarthritis can only be diagnosed by joint space narrowing when conventional radiography is used. This is due to the lack of X-ray contrast of soft tissues. Whereas conventional radiography harnesses the X-ray attenuation properties of tissues, Diffraction Enhanced Imaging (DEI), a novel radiographic technique, allows the visualization of soft tissues simultaneous with calcified tissues by virtue of its ability to not only harness X-ray attenuation but also the X-ray refraction from tissue boundaries. Previously, DEI was dependent upon synchrotron X-rays, but more recently, the development of nonsynchrotron DEI units has been explored. These developments serve to elaborate the full potential of radiography. Here, we tested the potential of an in-laboratory DEI system, called Diffraction-Enhanced X-ray Imaging (DEXI), to render images of articular cartilage displaying varying degrees of degradation, ex vivo. DEXI allowed visualization of even early stages of cartilage degeneration such as surface fibrillation. This may be of eventual clinical significance for the diagnosis of early stages of degeneration, or at the very least, to visualize soft tissue degeneration simultaneous with bone changes.

Diffraction-enhanced imaging for Achilles tendon lesions: a preliminary study.

BACKGROUND: Computed tomography, ultrasonography, and magnetic resonance imaging are useful in the diagnosis of tears of the Achilles tendon, but none are capable of detecting early or small tears. Herein, we applied diffraction-enhanced imaging, a radiographic technique that detects x-ray attenuation and x-ray refraction, to the imaging of compromised Achilles tendons. METHODS: Diffraction-enhanced imaging was used to detect incomplete surgically induced tears of the Achilles tendon in nine cadaveric human feet and ankles. RESULTS: Complete and significant partial tears were detectable in diffraction-enhanced images as x-ray refraction changes. CONCLUSIONS: Although still in the experimental stages, diffraction-enhanced imaging may eventually prove useful for the diagnosis of Achilles tendon tears.

Short Link N promotes disc repair in a rabbit model of disc degeneration.

BACKGROUND: The degeneration of the intervertebral disc (IVD) is characterized by proteolytic degradation of the extracellular matrix, and its repair requires the production of an extracellular matrix with a high proteoglycan-to-collagen ratio characteristic of a nucleus pulposus (NP)-like phenotype in vivo. At the moment, there is no medical treatment to reverse or even retard disc degeneration. The purpose of the present study was to determine if a low dose of short link N (sLN), a recently discovered fragment of the link N peptide, could behave in a manner similar to that of link N in restoring the proteoglycan content and proteoglycan-to-collagen ratio of the disc in a rabbit model of IVD degeneration, as an indication of its potential therapeutic benefit in reversing disc degeneration. METHODS: Adolescent New Zealand white rabbits received an annular puncture with an 18-gauge needle into two noncontiguous discs to induce disc degeneration. Two weeks later, either saline (10 µL) or sLN (25 µg in 10 µL saline) was injected into the center of the NP. The sLN concentration was empirically chosen at a lower molar concentration equivalent to half that of link N (100 µg in 10 µL). The effect on radiographic, biochemical and histologic changes were evaluated. RESULTS: Following needle puncture, disc height decreased by about 25-30% within 2 weeks and maintained this loss for the duration of the 12-week study; a single 25-µg sLN injection at 2 weeks partially restored this loss in disc height. sLN injection led to an increase in glycosaminoglycans (GAG) content 12 weeks post-injection in both the NP and annulus fibrosus (AF). There was a trend towards maintaining control disc collagen-content with sLN supplementation and the GAG-to-collagen ratio in the NP was increased when compared to the saline group. CONCLUSIONS: When administered to the degenerative disc in vivo, sLN injection leads to an increase in proteoglycan content and a trend towards maintaining control disc collagen content in both the NP and AF. This is similar to link N when it is administered to the degenerative disc. Thus, pharmacologically, sLN supplementation could be a novel therapeutic approach for treating disc degeneration.

Structural and biochemical evaluation of the elbow capsule after trauma.

This study evaluates the structural and biochemical alterations of the elbow capsule after trauma through microscopy and immunohistochemistry. We compared capsules from 37 patients undergoing surgery for elbow contracture with normal capsules from 7 donors. Contracture capsules were significantly thicker than control capsules (P < .05) and exhibited extensive disorganization of collagen fiber bundle arrangement. Levels of specific cytokines involved in connective tissue turnover were measured. The results showed that the levels of cytokines matrix metalloproteinase (MMP) 1, MMP-2, and MMP-3 were greater as compared with control capsules (P < .05). This was associated with collagen disorganization, fibroblast infiltration, and in some specimens, lymphocytic infiltration in the capsular tissue. In contracture specimens, there was a localization of tissue inhibitor of matrix metalloproteinase 2 staining only in the vicinity of the synovial membrane and in blood vessels. Immunohistochemistry for type III collagen showed a greater presence in the control capsules compared with contracture capsules. This study demonstrates pathologic thickening, disorganization of the collagen fiber arrangement, and involvement of cytokines in the pathology of post-traumatic contracture of the elbow.

A computed tomography implementation of multiple-image radiography.

Conventional x-ray computed tomography (CT) produces a single volumetric image that represents the spatially variant linear x-ray attenuation coefficient of an object. However, in many situations, differences in the x-ray attenuation properties of soft tissues are very small and difficult to measure in conventional x-ray imaging. In this work, we investigate an analyzer-based imaging method, called computed tomography multiple-image radiography (CT-MIR), which is a tomographic implementation of the recently proposed multiple-image radiography method. The CT-MIR method reconstructs concurrently three physical properties of the object. In addition to x-ray attenuation, CT-MIR produces volumetric images that represent the refraction and ultrasmall-angle scattering properties of the object. These three images can provide a rich description of the object's physical properties that are revealed by the probing x-ray beam. An imaging model for CT-MIR that is based on the x-ray transform of the object properties is established. The CT-MIR method is demonstrated by use of experimental data acquired at a synchroton radiation imaging beamline, and is compared to the pre-existing diffraction-enhanced imaging CT method. We also investigate the merit of an iterative reconstruction method for use with future clinical implementations of CT-MIR, which we anticipate would be photon limited.

Characterization of lesions of the talus and description of tram-track lesions.

BACKGROUND: The ankle joint, although not prone to primary osteoarthritis (OA), is known to be susceptible to secondary OA as a result of sports injuries and other trauma. Unlike the knee joint, a thorough investigation of talar cartilage lesions has not been previously reported. METHODS: One hundred and five human tali from 67 donors were used to determine the type and location of the most common lesions through gross examination, radiography, diffraction enhanced imaging, and histology. "tram-track lesions" also are described. RESULTS: The most anterior and posterior regions of the talar dome, along with the medial and lateral borders of the dome were most affected by cartilage degeneration. These are regions that appear to be most subjected to frictional forces from their articulating counterparts during high stress activities that move articulating surfaces slightly out of congruence with each other. One particularly striking cartilage degeneration pattern that, to our knowledge, has not been described histologically, is the tram-track lesion. These lesions displayed a longitudinally oriented groove in the cartilage, running from anterior to posterior, in which the deepest portion of the groove was located in the middle of the anterior-posterior axis of the talus. Several of these cartilage grooves had a bony ridge beneath, mirroring the cartilage groove whereas others did not. This suggests that the cartilage groove develops before the interruption of the tidemark (border between the calcified and uncalcified cartilage). In specimens for which the articulating tibial articular surface was available, (17) it was found that the tibia displayed small osteophytes on the anterior articular margin that exactly corresponded to their articulation with the talar cartilage grooves as the ankle articulated through plantar flexion and dorsiflexion. CONCLUSION: This study provides an in-depth histologic and gross anatomic look at the most common lesions of the talus of the ankle joint. In particular, the "tram-track" lesion was shown to be a consequence of its tibial articulation and to include both subchondral bone and articular cartilage changes.

Immunohistochemical localization of osteogenetic protein (OP-1) and its receptors in rabbit articular cartilage.

We assessed the distribution and relative immunohistochemical staining intensity of the bone morphogenetic protein-7, osteogenic protein-1 (OP-1), in its pro- and mature forms, and four of its receptors, type I (ALK-2, ALK-3, and ALK-6) and type II in normal adolescent New Zealand White rabbit articular cartilage. Expression of the protein and its receptors was also examined in cartilage from joints that had been previously subjected to cartilage matrix degradation. Pro-OP-1 was moderately expressed in chondrocytes of the superficial, middle, and deep cartilage zones and in the osteocytes. The expression of mature OP-1 was similar, with the exception of less staining in the superficial zone of cartilage. Expression of these two forms of OP-1 was enhanced in the middle and deep cartilage zones after catabolic challenge. The type I receptor, ALK-6, displayed the strongest staining of the receptors in both cartilage and bone, whereas ALK-2 displayed the weakest staining. No differences were observed in the receptor staining levels after catabolic challenge. This study shows that OP-1 and its receptors have been identified in rabbit articular cartilage and bone, suggesting a possible role for this pathway in cartilage and bone homeostasis.

Radiography of rabbit articular cartilage with diffraction-enhanced imaging.

Articular cartilage of synovial joints is not visible with conventional X-ray imaging. Hence, the gradual degeneration and destruction of articular cartilage, which is characteristic of degenerative joint diseases, is only detected at a late stage when the cartilage is lost and the joint space that it once occupied narrows. The development of an X-ray imaging technique that could detect both the degenerative cartilage and bone features of joint diseases is of special interest. Here we show, for the first time, that a high-contrast imaging technique, diffraction-enhanced X-ray imaging (DEI), allows the visualization of articular cartilage of both disarticulated and articulated rabbit knee joints. Furthermore, a single cartilage lesion can be visualized within an intact joint. The results suggest that DEI has the potential to be of use in the study of cartilage degeneration.

Multiple-image radiography.

Conventional radiography produces a single image of an object by measuring the attenuation of an x-ray beam passing through it. When imaging weakly absorbing tissues, x-ray attenuation may be a suboptimal signature of disease-related information. In this paper we describe a new phase-sensitive imaging method, called multiple-image radiography (MIR), which is an improvement on a prior technique called diffraction-enhanced imaging (DEI). This paper elaborates on our initial presentation of the idea in Wernick et al (2002 Proc. Int. Symp. Biomed. Imaging pp 129-32). MIR simultaneously produces several images from a set of measurements made with a single x-ray beam. Specifically, MIR yields three images depicting separately the effects of refraction, ultra-small-angle scatter and attenuation by the object. All three images have good contrast, in part because they are virtually immune from degradation due to scatter at higher angles. MIR also yields a very comprehensive object description, consisting of the angular intensity spectrum of a transmitted x-ray beam at every image pixel, within a narrow angular range. Our experiments are based on data acquired using a synchrotron light source; however, in preparation for more practical implementations using conventional x-ray sources, we develop and evaluate algorithms designed for Poisson noise, which is characteristic of photon-limited imaging. The results suggest that MIR is capable of operating at low photon count levels, therefore the method shows promise for use with conventional x-ray sources. The results also show that, in addition to producing new types of object descriptions, MIR produces substantially more accurate images than its predecessor, DEI. MIR results are shown in the form of planar images of a phantom and a biological specimen. A preliminary demonstration of the use of MIR for computed tomography is also presented.

Refraction effects of diffraction-enhanced radiographic imaging: a new look at bone.

The objective of this study was to demonstrate the ability of a novel radiographic technology-diffraction-enhanced imaging-to detect contrast in bone tissue through absorption, refraction, and scatter rejection. Diffraction-enhanced imaging uses a synchrotron x-ray beam to produce images of high contrast by measuring the object's refraction and ultra-small angle scattering of x-rays in addition to the attenuation measured by conventional radiography. We present evidence that diffraction-enhanced imaging provides contrast enhancement at the edges of cortical and cancellous bone and a three-dimensional appearance of trabeculae.

Subchondral thickness does not vary with cartilage degeneration on the metatarsal.

Osteoarthritis is a disease of synovial joints that involves articular cartilage breakdown with accompanying bone changes, including subchondral sclerosis and osteophytosis. However, conflicting data have been reported concerning the cause-and-effect relationship, if any, between these changes. The authors studied the subchondral plate (subchondral bone plus calcified cartilage) in relation to the degree of articular cartilage degeneration on the distal articular surface of the first metatarsal, a region prone to osteoarthritis. No correlation was found between subchondral plate thickness or porosity and the degree of cartilage degeneration in the study sample of 96 metatarsals. Owing to the suggestion that initiation of cartilage fibrillation may be a result of steep stiffness gradients in the subchondral bone, the ratios of subchondral plate thickness in adjacent regions of the metatarsal head were examined in detail, but no correlation was found with subchondral degeneration. Thus increases in subchondral bone thickness are not associated with increases in cartilage degeneration on the first metatarsal, which may imply that subchondral bone changes do not cause osteoarthritis in this joint.

Radiography of soft tissue of the foot and ankle with diffraction enhanced imaging.

Non-calcified tissues, including tendons, ligaments, adipose tissue and cartilage, are not visible, for any practical purposes, with conventional X-ray imaging. Therefore, any pathological changes in these tissues generally necessitate detection through magnetic resonance imaging or ultrasound technology. Until recently the development of an X-ray imaging technique that could detect both bone and soft tissues seemed unrealistic. However, the introduction of diffraction enhanced X-ray imaging (DEI) which is capable of rendering images with absorption, refraction and scatter rejection qualities has allowed detection of specific soft tissues based on small differences in tissue densities. Here we show for the first time that DEI allows high contrast imaging of soft tissues, including ligaments, tendons and adipose tissue, of the human foot and ankle.

Noise and analyzer-crystal angular position analysis for analyzer-based phase-contrast imaging.

The analyzer-based phase-contrast x-ray imaging (ABI) method is emerging as a potential alternative to conventional radiography. Like many of the modern imaging techniques, ABI is a computed imaging method (meaning that images are calculated from raw data). ABI can simultaneously generate a number of planar parametric images containing information about absorption, refraction, and scattering properties of an object. These images are estimated from raw data acquired by measuring (sampling) the angular intensity profile of the x-ray beam passed through the object at different angular positions of the analyzer crystal. The noise in the estimated ABI parametric images depends upon imaging conditions like the source intensity (flux), measurements angular positions, object properties, and the estimation method. In this paper, we use the Cramér-Rao lower bound (CRLB) to quantify the noise properties in parametric images and to investigate the effect of source intensity, different analyzer-crystal angular positions and object properties on this bound, assuming a fixed radiation dose delivered to an object. The CRLB is the minimum bound for the variance of an unbiased estimator and defines the best noise performance that one can obtain regardless of which estimation method is used to estimate ABI parametric images. The main result of this paper is that the variance (hence the noise) in parametric images is directly proportional to the source intensity and only a limited number of analyzer-crystal angular measurements (eleven for uniform and three for optimal non-uniform) are required to get the best parametric images. The following angular measurements only spread the total dose to the measurements without improving or worsening CRLB, but the added measurements may improve parametric images by reducing estimation bias. Next, using CRLB we evaluate the multiple-image radiography, diffraction enhanced imaging and scatter diffraction enhanced imaging estimation techniques, though the proposed methodology can be used to evaluate any other ABI parametric image estimation technique.

Limited-angle tomography for analyzer-based phase-contrast x-ray imaging.

Multiple-image radiography (MIR) is an analyzer-based phase-contrast x-ray imaging method, which is emerging as a potential alternative to conventional radiography. MIR simultaneously generates three planar parametric images containing information about scattering, refraction and attenuation properties of the object. The MIR planar images are linear tomographic projections of the corresponding object properties, which allows reconstruction of volumetric images using computed tomography (CT) methods. However, when acquiring a full range of linear projections around the tissue of interest is not feasible or the scanning time is limited, limited-angle tomography techniques can be used to reconstruct these volumetric images near the central plane, which is the plane that contains the pivot point of the tomographic movement. In this work, we use computer simulations to explore the applicability of limited-angle tomography to MIR. We also investigate the accuracy of reconstructions as a function of number of tomographic angles for a fixed total radiation exposure. We use this function to find an optimal range of angles over which data should be acquired for limited-angle tomography MIR (LAT-MIR). Next, we apply the LAT-MIR technique to experimentally acquired MIR projections obtained in a cadaveric human thumb study. We compare the reconstructed slices near the central plane to the same slices reconstructed by CT-MIR using the full angular view around the object. Finally, we perform a task-based evaluation of LAT-MIR performance for different numbers of angular views, and use template matching to detect cartilage in the refraction image near the central plane. We use the signal-to-noise ratio of this test as the detectability metric to investigate an optimum range of tomographic angles for detecting soft tissues in LAT-MIR. Both results show that there is an optimum range of angular view for data acquisition where LAT-MIR yields the best performance, comparable to CT-MIR only if one considers volumetric images near the central plane and not the whole volume.

Histological features of endplates of the mammalian spine: from mice to men.

STUDY DESIGN: Histological features of the intervertebral disc (IVD)-endplate interface were analyzed. OBJECTIVE: To define cartilaginous and bony vertebral endplate in commonly used laboratory animals and compare with that of the humans. SUMMARY OF BACKGROUND DATA: Endplates are crucial for the IVD nutrient supply: the IVDs have limited blood supply; most nutrients diffuse through endplates to nourish the discs. Various animal models of IVD and endplate degeneration have been used to study the etiology and treatments of spinal disorders. However, because humans are biped, the spine mechanics differ significantly from other mammals. Translation of animal research findings requires a characterization and comparison of the vertebral endplate in the respective species. In this study, we compared the endplate structure of laboratory animal species at the age range commonly used for modeling spine degeneration with that of an adult human. METHODS: Mouse, rat, rabbit, goat, and human IVDs and the adjacent vertebral bodies were isolated from the lower lumbar spine. Tissues were stained with Alcian Blue, counterstained with hematoxylin and eosin. RESULTS: Structure of the vertebral endplate varied significantly between the adult animal species and that of the humans. Growth plates persisted in all adult animals studied, whereas the growth plate is absent in the adult humans. In the mice and rats, the cartilaginous endplates are in continuation with the growth plates, with only a small bony center. Rabbits and goats have a bony layer between cartilaginous endplate and the growth plate. The human endplate consist of a cartilaginous layer and the bony endplate. CONCLUSION: Significant differences exist in histological features of the endplate across animal species and that of the humans. Consideration should be given when animal models are used to study IVD degeneration and surgical treatments. LEVEL OF EVIDENCE: 5.