Degrees Of Disc Degeneration Research Articles

Comparative Analysis of Autophagy and Apoptosis in Disc Degeneration: Understanding the Dynamics of Temporary-Compression-Induced Early Autophagy and Sustained-Compression-Triggered Apoptosis.

The purpose of this study was to investigate the initiation of autophagy activation and apoptosis in nucleus pulposus cells under temporary compression (TC) and sustained compression (SC) to identify ideal research approaches in intervertebral disc degeneration. Various techniques were used: radiography (X-ray), magnetic resonance imaging (MRI), transmission electron microscope (TEM), H&E staining, Masson's trichrome staining, immunohistochemistry (IHC) (LC3, beclin-1, and cleaved caspase-3), and real-time polymerase chain reaction (RT-qPCR) for autophagy-related (beclin-1, LC3, and P62) and apoptosis-related (caspase-3 and PARP) gene expression analysis. X-ray and MRI revealed varying degrees of disc degeneration, ranging from moderate to severe in both groups. The severity was directly linked to compression duration, with SC resulting in notably severe central NP cell degeneration. Surprisingly, TC also caused similar, though less severe, degeneration. Elevated expression of LC3 and beclin-1 was identified after 6 weeks, but it notably declined after 12 weeks. Central NP cells in both groups exhibited increased expression of cleaved caspase-3 that was positively correlated with the duration of SC. TC showed fewer apoptotic markers compared to SC. LC3, beclin-1, and P62 mRNA expression peaked after 6 weeks and declined after 12 weeks in both groups. Cleaved caspase-3 and PARP expression peaked in SC, positively correlating with longer compression duration, while TC showed lower levels of apoptosis gene expression. Furthermore, TEM results revealed different events of the autophagic degradation process after 2 weeks of compression. TCmay be ideal for studying early triggered autophagy-mediated degeneration, while SC may be ideal for studying late or slower-triggered apoptosis-mediated degeneration.

P8. Responsiveness of patient derived intervertebral disc cells to mechanobiological treatment

P8. Responsiveness of patient derived intervertebral disc cells to mechanobiological treatment

Is There Any Association between the Severity of Disc Degeneration and Low Back Pain?

Objective To access the possibility that higher degrees of disc degeneration lead to higher levels of pain and dysfunction. Methods Magnetic resonance imaging (MRI) scans of 85 patients with low back pain lasting for more than 12 weeks were evaluated, and the degree of disc degeneration was quantified according to the Pfirrmann grading system. The Pfirrmann degree in each disc space from L1-L2 to L5-S1, the maximum degree of Pfirrmann (Pfirrmann-max) between the lumbar discs, and the sum of Pfirrmann (Pfirrmann-sum) degrees were correlated (through the Spearman test) with the Oswestry Disability Index (ODI) and the Visual Analogical Scale (VAS) for pain. Results In total, 87% of the patients had moderate to severe lumbar disc degeneration measured by Pfirrmann-max, and the most degenerated discs were L4-L5 and L5-S1. There was a week to moderate correlation regarding the Pfirrmann-max (r = 0,330; p = 0.002) and the Pfirrmann-sum (r = 0,266; p = 0,037) and the ODI, and the Pfirrmann scores in L1-L2 were correlated with the ODI and the VAS. Conclusion Patients with chronic idiopathic low back pain frequently have moderate to severe lumbar disc degeneration, which has a negative impact on the quality of life of the patients. Low degrees of degeneration in L1-L2 might be related with higher degrees of pain and of functional disability.

Biomechanical Contributions of Spinal Structures with Different Degrees of Disc Degeneration.

Biomechanical cadaveric study. The aim of this study was to evaluate the effect of degeneration on biomechanical properties of the passive structures of the lumbar spine. Although the load apportionment among the passive structures in healthy spines follows well-defined contribution patterns, it remains unknown how this load distribution and sagittal preload changes by degenerative processes of the intervertebral disc (IVD). Fifty lumbar spinal segments were tested in a displacement-controlled stepwise reduction study in flexion, extension, axial rotation, lateral bending, anterior, posterior and lateral shear. The intertransverse ligaments (ITLs), supraspinous and interspinous ligaments (ISL&SSL), facet joint capsules (FJC), facet joints (FJ), ligamentum flavum (LF), posterior longitudinal ligament (PLL), anterior longitudinal ligament (ALL), and spondylophytes were subsequently reduced. The results were set in relation to IVD-degeneration, quantified with Pfirrmann classification. In flexion, a load redistribution from LF (-28% n.s.) and PLL (-13% n.s.) towards the IVD (+9%, n.s.) is observed comparing grade 2 to 5 IVD degeneration, whereas in all other loading directions, a reduction of IVD-contribution from -12% to -53% is recorded. In axial rotation, anterior and lateral shear, more load is shared by the FJ (+4% n.s., +23% ∗, +13% n.s.). The preload of the ALL, LF, PLL, and IVD is reduced ranging from -0.06 Nm to -0.37 Nm. IVD degeneration is related to notable load-redistributions between the passive spinal structures. With further degeneration, reduced contribution of the LF and PLL and higher loads on the IVD are observed in flexion. In the other tested loading directions, the relative load on the IVD is reduced, whereas higher FJ-exposure in axial rotation, anterior and lateral shear is observed. Furthermore, the preload of the spinal structures is reduced. These observations can further the understanding of the degenerative cascade in the spine.Level of Evidence: N/A.

Lumbar spinal stenosis and disc alterations affect the upper lumbar spine in adults with achondroplasia

In achondroplasia, lumbar spinal stenosis arises from congenital dysplasia and acquired degenerative changes. We here aimed to describe the changes of the lumbar spinal canal and intervertebral disc in adults. We included 18 adults (age ≥ 18 years) with achondroplasia and lumbar spinal stenosis. Radiographs were used to analyze spinal-pelvic angles. Antero-posterior diameter of the spinal canal and the grade of disc degeneration were measured by MRI. Antero-posterior diameters of the spinal canal differed by spinal level (P < 0.05), with lower values observed at T12-L1, L1-2 and L2-3. Degrees of disc degeneration differed by intervertebral level, with higher degrees observed at L1-2, L2-3 and L3-4. A significant correlation was found between disc degeneration and thoraco-lumbar kyphosis at L2-3, between antero-posterior diameter of the spinal canal and lumbar lordosis at T12-L1 and L2-3, and between antero-posterior diameter of the spinal canal and thoraco-lumbar kyphosis at L1-2. Unlike the general population, spinal stenosis and disc degeneration involve the upper part of the lumbar spine in adults with achondroplasia, associated with thoraco-lumbar kyphosis and loss of lumbar lordosis.

Anterior cervical hybrid fusion and arthroplasty

Cervical disc arthroplasty may not be suitable for patients with symptomatic multilevel cervical disc degeneration given its relatively narrow indication. A long-construct fusion, however, may not be optimal given the prevalence of adjacent segment pathology following fusion. Moreover, patients may have varying degrees of disc degeneration, some of which may be adequately addressed by arthroplasty rather than fusion. Hybrid surgery (HS), which involves the combination of ACDF and CDA, has been increasingly utilized over fusion alone for patients with symptomatic multilevel disc degeneration. The combination of fusion with arthroplasty aims to preserve segmental motion at the index levels while minimizing adjacent-level hypermobility compared to ACDF alone.

Cartilage Endplate Thickness Variation Measured by Ultrashort Echo-Time MRI Is Associated With Adjacent Disc Degeneration.

A magnetic resonance imaging study of human cadaver spines. To investigate associations between cartilage endplate (CEP) thickness and disc degeneration. Damage to the CEP is associated with spinal injury and back pain. However, CEP morphology and its association with disc degeneration have not been well characterized. Ten lumbar motion segments with varying degrees of disc degeneration were harvested from six cadaveric spines and scanned with magnetic resonance imaging in the sagittal plane using a T2-weighted two-dimensional (2D) sequence, a three-dimensional (3D) ultrashort echo-time (UTE) imaging sequence, and a 3D T1ρ mapping sequence. CEP thicknesses were calculated from 3D UTE image data using a custom, automated algorithm, and these values were validated against histology measurements. Pfirrmann grades and T1ρ values in the disc were assessed and correlated with CEP thickness. The mean CEP thickness calculated from UTE images was 0.74 ± 0.04 mm. Statistical comparisons between histology and UTE-derived measurements of CEP thickness showed significant agreement, with the mean difference not significantly different from zero (P = 0.32). Within-disc variation of T1ρ (standard deviation) was significantly lower for Pfirrmann grade 4 than Pfirrmann grade 3 (P < 0.05). Within-disc variation of T1ρ and adjacent CEP thickness heterogeneity (coefficient of variation) had a significant negative correlation (r = -0.65, P = 0.04). The standard deviation of T1ρand the mean CEP thickness showed a moderate positive correlation (r = 0.40, P = 0.26). This study demonstrates that quantitative measurements of CEP thickness measured from UTE magnetic resonance imaging are associated with disc degeneration. Our results suggest that variability in CEP thickness and T1ρ, rather than their mean values, may serve as valuable diagnostic markers for disc degeneration. N/A.

Association Between Lumbar Spine Sagittal Alignment and L4-L5 Disc Degeneration Among Asymptomatic Young Adults.

Cross-sectional observational study on the relationship between the degrees of disc degeneration and sagittal alignment in asymptomatic healthy individuals. This study sought to determine whether the sagittal spine alignment subtype is related to the prevalence of lumbar disc degeneration. Sagittal balance and spinopelvic parameters might be risk factors for disc degeneration. A total of 70 asymptomatic participants (36 women and 34 men) without regular physical activity were categorized according to the four subtypes of sagittal alignment proposed by Roussouly. All participants underwent magnetic resonance imaging of the lumbar spine (1.5T) and panoramic radiography of the spine. The degree of disc degeneration was graded using T2-weighted images according to the Pfirrmann classification. Spinopelvic parameters and vertebral curvatures were measured on digital panoramic radiographs using Surgimap software. Interobserver analyses for the Pfirrmann classification and spinopelvic parameters were assessed using the weighted Kappa and intraclass correlation coefficient (ICC), respectively. The Kappa associated with disc degeneration classification was 0.79 (95% confidence intervals 0.72-0.87). The ICCs were excellent, with small confidence intervals for all spinopelvic parameters. The type II group (flat lordosis) showed a higher frequency of degenerated discs at L4-L5 (P = 0.03) than the type IV group (long and curved lumbar spine). No significant differences in disc degeneration were observed among the four subtypes at the other disc levels. We found a negative, moderate correlation between the spinopelvic parameters and the occurrence of disc degeneration in the type II group. The Roussouly subtype II sagittal alignment is significantly associated with disc degeneration at L4-L5 in asymptomatic young adults. Our results support the hypothesis that spinal sagittal alignment plays a role in early disc degeneration. 3.

A large animal model that recapitulates the spectrum of human intervertebral disc degeneration

The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics. Degeneration was induced in the lumbar intervertebral discs of large frame goats by either intradiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, microcomputed tomography (μCT), and measurement of disc biomechanical properties. Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1ρ, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical boney endplate adjacent to ChABC-injected discs also occurred. Spine segment range of motion (ROM) was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact. A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration.

Effects of resting modes on human lumbar spines with different levels of degenerated intervertebral discs: a finite element investigation.

BackgroundThe negative effect of long-term working load on lumbar is widely known. However, insertion of different resting modes on long-term working load, and its effects on the lumbar spine is rarely studied. The purpose of this study was to investigate the biomechanical responses of lumbar spine with different levels of degenerated intervertebral discs under different working-resting modes.MethodsFour poroelastic finite element models of lumbar spinal segments L2-L3 with different grades of disc degeneration were developed. Four different loading conditions represented four different resting frequencies, namely, no rest, one-time long rest, three-time moderate rests, and five-time short rests, on the condition that the total resting time was the same except in the no rest mode. Loading amplitudes of diurnal activities included 100 N, 300 N, and 500 N.ResultsWith increasing resting frequency, the axial effective stress and fluid loss decreased, whereas the pore pressure and radial displacement increased. Under different resting frequencies, the changing rate of each biomechanical parameter was different.ConclusionsUnder a situation of fixed total resting time, high resting frequency was advisable. If sufficient resting frequency was unavailable for healthy people as well as patients with mildly and moderately degenerated intervertebral discs, they could similarly benefit from relatively less resting frequencies. However, one-time rest will not be useful in cases where intervertebral discs were seriously degenerated. Reasonable working-resting modes for different degrees of disc degeneration, which could assist patients achieve a better restoration, were provided in this study.

Ligamentum Flavum Hypertrophy in Asymptomatic and Chronic Low Back Pain Subjects

PurposeTo examine ligamentum flavum thickness using magnetic resonance (MR) images to evaluate its association with low back pain symptoms, age, gender, lumbar level, and disc characteristics.Materials and MethodsSixty-three individuals were part of this IRB-approved study: twenty-seven with chronic low back pain, and thirty-six as asymptomatic. All patients underwent MR imaging and computed tomography (CT) of the lumbar spine. The MR images at the mid-disc level were captured and enlarged 800% using a bilinear interpolation size conversion algorithm that allowed for enhanced image quality. Ligamentum flavum thickness was assessed using bilateral medial and lateral measurements. Disc height at each level was measured by the least-distance measurement method in three-dimensional models created by CT images taken of the same subject. Analysis of variance and t-tests were carried out to evaluate the relationship between ligamentum flavum thickness and patient variables.ResultsLigamentum flavum thickness was found to significantly increase with older age, lower lumbar level, and chronic low back pain (p < 0.03). No difference in ligamentum flavum thickness was observed between right and left sided measurements, or between male and female subjects. Disc height and both ligamentum flavum thickness measurements showed low to moderate correlations that reached significance (p < 0.01). Additionally, a moderate and significant correlation between disc degeneration grade and ligamentum flavum thickness does exist (p <0.001).ConclusionBy measuring ligamentum flavum thickness on MR images at two different sites and comparing degrees of disc degeneration, we found that ligamentum flavum thickness may be closely related to the pathogenesis of pain processes in the spine.

Hypertension is Independently Associated with Lumbar Disc Degeneration: A Large-Scale Population-Based Study

Introduction Low back pain (LBP) is the most disabling condition in the world. Lumbar intervertebral disc degeneration is one of the risk factors for LBP. In particular, specific clinically relevant phenotypes of degeneration, such as moderate and severe degenerative changes, have been noted to increase the risk of the development of low back pain. Although progressive age, abnormal biomechanics, and genetics play a role in the development of disc degeneration, cardiovascular risk factors (e.g., age, smoking, obesity, etc.) have also been suggested to be determinants. Hypertension, manifesting as elevated systolic and/or diastolic blood pressure, is a factor related to cardiovascular disease; however, its role in the development of disc degeneration among a population remains speculative. As such, this large-scale population-based study addressed the association of blood pressure in relation to lumbar disc degeneration. Materials and Methods This was a cross-sectional study of the Hong Kong Disc Degeneration-Cardiovascular Cohort, currently composed of approximately 1,800 Southern Chinese volunteers. At the time of analyses, there were 1,261 subjects (36.6 males; 63.4% females) with a mean age of 52.4 years (range: 30-89; SD: ± 6.3 years). Serum lipid profile, glucose, ESR, and other blood parameters were assessed. Anthropomorphic and lifestyle/environmental (e.g., smoking, exercise, occupation) measurements as well as pain profiles were obtained of all subjects. Systolic and diastolic blood pressure assessment was conducted on three occasions. Hypertension was defined as systolic blood pressure of ≥ 140 mm Hg and/or diastolic pressure of ≥ 90 mm Hg. Medication use was accounted. Each subject had undergone T2-weighted MRI of the lumbar spine from L1-S1. Disc degeneration of each lumbar disc was assessed by the Schneiderman et al radiographic criteria. A summated degenerative disc disease (DDD) score was obtained of the entire lumbar spine. DDD score was used to denote subjects with normal, mild, medium, moderate, and severe degrees of disc degeneration. A DDD score of 5 of greater was regarded as a moderate/severe imaging phenotype of disc degeneration. Additional spinal imaging phenotypes (e.g., Modic changes, Schmorl nodes, etc.) were also assessed. Results Overall disc degeneration was present in 79% of all the subjects, most prevalent at L4-L5 (57.9%). Mean DDD score was 3.4 (range: 0-14; SD: ± 2.9 score). Mean systolic and diastolic measurements were 127.0 (range: 81-225; SD: ± 20.1 mm Hg) and 75.6 (range: 41-120; SD: ± 12.3 mm Hg), respectively. Mean systolic/diastolic values were significantly elevated in individuals with the overall presence of disc degeneration (mean: 127.6/76.0 mm Hg) compared with subjects with normal discs (mean: 124.3/73.9 mm Hg) ( p &lt; 0.001). Mean systolic/diastolic values were also significantly greater in individuals with moderate/severe disc degeneration (mean: 131.1/77.6 mm Hg) compared with those that had less severe grades of degeneration (mean: 125.1/74.62 mm Hg) ( p &lt; 0.001). Among the 1,261 subjects, 28% had hypertension. Hypertension was noted in 35.5% of those with moderate/severe disc degeneration compared with 24.5% with less severe degenerative profiles ( p &lt; 0.001). Based on a multivariate regression model adjusting for age, Modic changes, Schmorl nodes, diabetes, ESR, and LBP status, hypertension was significantly related to moderate/severe disc degeneration (OR: 1.51; 95% CI: 1.05-2.17; p = 0.027). Conclusion Based on one of the largest population-based studies addressing imaging, environmental/lifestyle, and cardiovascular risk factors, this study has illustrated for the first time that elevated blood pressure is “independently” associated with different stages of lumbar disc degeneration on MRI. Hypertension increases the likelihood of moderate/severe disc degeneration, a phenotype highly associated with LBP, by 50%. In an age where people are becoming less physically active and more overweight/obese, the prevalence of cardiovascular risk factors will continue to increase. As such, this study raises further awareness of the potential role of vascular disease in a “predictive risk profile model” of lumbar disc degeneration. Disclosure of Interest None declared

Regional variations in trabecular architecture of the lumbar vertebra: Associations with age, disc degeneration and disc space narrowing

Previous studies suggest that age and disc degeneration are associated with variations in vertebral trabecular architecture. In particular, disc space narrowing, a severe form of disc degeneration, may predispose the anterior portion of a vertebra to fracture. We studied 150 lumbar vertebrae and 209 intervertebral discs from 48 cadaveric lumbar spines of middle-aged men to investigate regional trabecular differences in relation to age, disc degeneration and disc narrowing. The degrees of disc degeneration and narrowing were evaluated using radiography and discography. The vertebrae were dried and scanned on a μCT system. The μCT images of each vertebral body were processed to include only vertebral trabeculae, which were first divided into superior and inferior regions, and further into central and peripheral regions, and then anterior and posterior regions. Structural analyses were performed to obtain trabecular microarchitecture measurements for each vertebral region. On average, the peripheral region had 12–15% greater trabecular bone volume fraction and trabecular thickness than the central region (p<0.01). Greater age was associated with better trabecular structure in the peripheral region relative to the central region. Moderate and severe disc degeneration were associated with higher trabecular thickness in the peripheral region of the vertebral trabeculae (p<0.05). The anterior region was of lower bone quality than the posterior region, which was not associated with age. Slight to moderate narrowing was associated with greater trabecular bone volume fraction in the anterior region of the inferior vertebra (p<0.05). Similarly, greater disc narrowing was associated with higher trabecular thickness in the anterior region (p<0.05). Better architecture of peripheral trabeculae relative to central trabeculae was associated with both age and disc degeneration. In contrast to the previous view that disc narrowing stress-shields the anterior vertebra, disc narrowing tended to associate with better trabecular architecture in the anterior region, as opposed to the posterior region.

Applications of finite element simulation in orthopedic and trauma surgery

Research in different areas of orthopedic and trauma surgery requires a methodology that allows both a more economic approach and the ability to reproduce different situations in an easy way. Simulation models have been introduced recently in bioengineering and could become an essential tool in the study of any physiological unity, regardless of its complexity. The main problem in modeling with finite elements simulation is to achieve an accurate reproduction of the anatomy and a perfect correlation of the different structures, in any region of the human body. Authors have developed a mixed technique, joining the use of a three-dimensional laser scanner Roland Picza captured together with computed tomography (CT) and 3D CT images, to achieve a perfect reproduction of the anatomy. Finite element (FE) simulation lets us know the biomechanical changes that take place after hip prostheses or osteosynthesis implantation and biological responses of bone to biomechanical changes. The simulation models are able to predict changes in bone stress distribution around the implant, so allowing preventing future pathologies. The development of a FE model of lumbar spine is another interesting application of the simulation. The model allows research on the lumbar spine, not only in physiological conditions but also simulating different load conditions, to assess the impact on biomechanics. Different degrees of disc degeneration can also be simulated to determine the impact on adjacent anatomical elements. Finally, FE models may be useful to test different fixation systems, i.e., pedicular screws, interbody devices or rigid fixations compared with the dynamic ones. We have also developed models of lumbar spine and hip joint to predict the occurrence of osteoporotic fractures, based on densitometric determinations and specific biomechanical models, including approaches from damage and fracture mechanics. FE simulations also allow us to predict the behavior of orthopedic splints applied to the correction of deformities, providing the recovering force-displacement and angle-moment curves that characterize the mechanical behavior of the splint in the overall range of movement.

Kinematic Evaluation of Association between Disc Bulge Migration, Lumbar Segmental Mobility, and Disc Degeneration in the Lumbar Spine Using Positional Magnetic Resonance Imaging

Degenerative disc disease and disc bulge in the lumbar spine are common sources of lower back pain. Little is known regarding disc bulge migration and lumbar segmental mobility as the lumbar spine moves from flexion to extension. In this study, 329 symptomatic (low back pain with or without neurological symptoms) patients with an average age of 43.5 years with varying degrees of disc degeneration were examined to characterize the kinematics of the lumbar intervertebral discs through flexion, neutral, and extension weight-bearing positions. In this population, disc bulge migration associated with dynamic motion of the lumbar spine significantly increased with increased grade of disk degeneration. Although no obvious trends relating the migration of disc bulge and angular segmental mobility were seen, translational segmental mobility tended to increase with disc bulge migration in all of the degenerative disc states. It appears that many factors, both static (intervertebral disc degeneration or disc height) and dynamic (lumbar segmental mobility), affect the mechanisms of lumbar disc bulge migration.

Comparative Expression of Matrix-associated Genes and Inflammatory Cytokines-associated Genes According to Disc Degeneration

The 2 groups of living human nucleus pulposus were prospectively compared according to disc degeneration. This study was conducted to investigate the expressions of various genes associated with matrix synthesis and expressions of inflammatory cytokines-associated genes according to degrees of disc degeneration in human discs. Degenerated discs were obtained from 18 patients who underwent discectomy for lumbar disc herniation. Disc degeneration was graded by T2-weighted magnetic resonance imaging using Pfirrmann's grading system. Discs were allocated to 2 groups: group I (9 patients)-mildly degenerated discs (grades II and III) and group II (9 patients)-severely degenerated discs (grades IV and V). Cells from the nucleus pulposus were isolated and then cultured as monolayers. The mRNA expressions of aggrecan, type II collagen, Sox9, type I collagen, alkaline phosphatase, osteocalcin, tumor necrosis factor-α, and interleukin-1β in the 2 groups were compared by real-time polymerase chain reaction, and production of matrix-associate proteins (aggrecan, type II collagen, Sox9, type I collagen, alkaline phosphatase, and osteocalcin) were compared by Western blotting. mRNA expressions in group I were upregulated versus group II to the following extents: 1.83 times for aggrecan, 1.82 times for type II collagen, 1.80 times for Sox9, 1.41 times for type I collagen, 1.38 times for alkaline phosphatase, and 1.80 times for osteocalcin. Furthermore, Western blotting showed that aggrecan, type II collagen, Sox9, type I collagen, alkaline phosphatase, and osteocalcin were higher in group I. However, the mRNA levels of tumor necrosis factor-α and interleukin-1β were 1.26 and 1.11-fold, respectively, upregulated in group II. Mildly degenerated discs showed greater matrix, chondrogenic, and osteoblastic gene expressions than severely degenerated discs, indicating that the ability to produce matrix-associated proteins is greater for cells in mildly degenerated than in severely degenerated discs. However, inflammatory cytokine genes associated with disc degeneration were expressed at higher levels in the severely degenerated group. This study shows that a reduction in matrix synthesis and an increase of inflammatory cytokine levels occurs during disc degeneration at the same time.

Interactions of environmental conditions and mechanical loads have influence on matrix turnover by nucleus pulposus cells

Disc degeneration is associated with several changes in the physicochemical environment of intervertebral disc cells. Nucleus pulposus (NP) cells in the center of degenerated discs are exposed to decreased glucose supply, osmolarity, pH, and oxygen levels. To understand the complexity of these interactions on a cellular level, we designed standardized experiments in which we compared responses to these environmental factors under normal levels with those seen under two different degrees of disc degeneration. We hypothesized that these changes in environmental stimuli influence gene expression of matrix proteins and matrix degrading enzymes and alter their responses to cyclic hydrostatic pressure (HP). Our results suggest that a simulation of degenerative conditions influences the degradation of disc matrix through impairing matrix formation and accelerating matrix resorption via up- or down-regulation of the respective target genes. The greatest effects were seen for decreases in glucose concentration and pH. Low oxygen had little influence. HP had little direct effect but appeared to counteract matrix degradation by reducing or inverting some of the adverse effects of other stimuli. For ongoing in vitro studies, interactions between mechanical stimuli and factors in the physicochemical environment should not be ignored as these could markedly influence results.

Quantitative T2 evaluation at 3.0 T compared to morphological grading of the lumbar intervertebral disc: A standardized evaluation approach in patients with low back pain

The purpose of our investigation was to compare quantitative T2 relaxation time measurement evaluation of lumbar intervertebral discs with morphological grading in young to middle-aged patients with low back pain, using a standardized region-of-interest evaluation approach. Three hundred thirty lumbar discs from 66 patients (mean age, 39 years) with low back pain were examined on a 3.0T MR unit. Sagittal T1-FSE, sagittal, coronal, and axial T2-weighted FSE for morphological MRI, as well as a multi-echo spin-echo sequence for T2 mapping, were performed. Morphologically, all discs were classified according to Pfirrmann et al. Equally sized rectangular regions of interest (ROIs) for the annulus fibrosus were selected anteriorly and posteriorly in the outermost 20% of the disc. The space between was defined as the nucleus pulposus. To assess the reproducibility of this evaluation, inter- and intraobserver statistics were performed. The Pfirrmann scoring of 330 discs showed the following results: grade I: six discs (1.8%); grade II: 189 (57.3%); grade III: 96 (29.1%); grade IV: 38 (11.5%); and grade V: one (0.3%). The mean T2 values (in milliseconds) for the anterior and the posterior annulus, and the nucleus pulposus for the respective Pfirrmann groups were: I: 57/30/239; II: 44/67/129; III: 42/51/82; and IV: 42/44/56. The nucleus pulposus T2 values showed a stepwise decrease from Pfirrmann grade I to IV. The posterior annulus showed the highest T2 values in Pfirrmann group II, while the anterior annulus showed relatively constant T2 values in all Pfirrmann groups. The inter- and intraobserver analysis yielded intraclass correlation coefficients (ICC) for average measures in a range from 0.82 (anterior annulus) to 0.99 (nucleus). Our standardized method of region-specific quantitative T2 relaxation time evaluation seems to be able to characterize different degrees of disc degeneration quantitatively. The reproducibility of our ROI measurements is sufficient to encourage the use of this method in future investigations, particularly for longitudinal studies.

Dependency of disc degeneration on shear and tensile strains between annular fiber layers for complex loads

Background One of the first signs of disc degeneration is the formation of circumferential tears within the annulus fibrosus. It is assumed that high shear and tensile strains between the lamellae mainly cause the initiation of these failures. However, it is not known which load application and which degree of disc degeneration could lead to the highest strains and therefore, might induce the formation of tears. Therefore, the aim of this finite element (FE) study was, to find load combinations that would yield highest shear and tensile strains in differently degenerated discs. Materials and methods A three-dimensional FE-model of a motion segment L4-5 was utilized in different degrees of disc degeneration (healthy, mild, moderate, and severe). The degenerated models consider the reduction of disc height, endplate curvatures, the osteophyte formation, the increase of nucleus compressibility, and the decrease of fiber and ligament stiffness. An axial compression load of 500 N together with moments of 7.5 Nm in single and combined load directions were simulated. Results High strains for the healthy and degenerated discs were predicted for load combinations, particularly for the combination of lateral bending plus flexion or extension. The maximum strains were located in the postero-lateral region of the disc. In comparison to the healthy disc, the maximum strains increased slightly for the mildly and moderately degenerated disc. Strains decreased strongly for the severely degenerated disc. With progressive degeneration, the size of the region of maximum strains diminished and the location transferred from the inner annulus to the adjacent bony endplates. Conclusions The results could be a possible explanation for the initiation of circumferential tears. The mildly degenerated disc model, which represents early stages of life, suggests that circumferential tears could primarily occur at these stages, especially for the load combinations of lateral bending plus axial rotation and lateral bending plus flexion.

Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological findings in 500 en bloc surgical samples

In this paper the authors' goal was to identify histological and immunohistochemical differences between cervical disc hemrniation and spondylosis. A total of 500 cervical intervertebral discs were excised from 364 patients: 198 patients with disc herniation and 166 patients with spondylosis. We examined en bloc samples of endplate-ligament-disc complexes. Types of herniation and graded degrees of disc degeneration on MR images were examined histologically and immunohistochemically. The herniated discs showed granulation tissue, newly developed blood vessels, and massive infiltration of CD68-positive macrophages, which surrounded the herniated tissue mainly in the ruptured outer layer of the anulus fibrosus. The vascular invasion was most significant in uncontained (extruded)-type herniated discs. Chondrocytes positive for matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-alpha, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were abundant in both herniated and spondylotic discs. Free nerve fibers, positive for nerve growth factor (NGF), neurofilament 68, growth-associated protein (GAP)-43, and substance P, were strongly apparent in and around the outer layer of uncontained (extruded)-type herniated discs, with enhanced expression of NGF. The authors observed that herniated discs showed more advanced degeneration in the outer layer of the anulus fibrosus around the granulation tissue than spondylotic discs. On the other hand, spondylotic discs showed more advanced degeneration in the cartilaginous endplate and inner layer of the anulus fibrosus than herniated discs. Spondylotic discs also had thicker bony endplates and expressed TNFalpha and MMP-3 more diffusely than herniated discs, especially in the inner layer of the anulus fibrosus. The authors' results indicate that herniated and spondylotic intervertebral discs undergo different degenerative processes. It is likely that TNFa, MMP-3, bFGF, and VEGF expression is upregulated via the herniated mass in the herniated intervertebral discs, but by nutritional impairment in the spondylotic discs. Macrophage accumulation around newly formed blood vessels in the herniated disc tissues seemed to be regulated by MMP-3 and TNFalpha expression, and both herniated and spondylotic discs exhibited marked neoangiogenesis associated with increased bFGF and VEGF expression. Nerve fibers were associated with NGF overexpression in the outer layer of the anulus fibrosus as well as in endothelial cells of the small blood vessels.