Immunolocalization of type X collagen in human lumbar intervertebral discs during ageing and degeneration

 Type X collagen has so far not been reported to occur in human intervertebral discs. The objective of this study was therefore to investigate the occurrence of type X collagen in human lumbar intervertebral discs during ageing and degeneration. Ninety intervertebral discs with adjacent endplates were excised in toto from individuals (0–86 years) without known spinal disease and were processed for routine decalcified histology. Appropriate slices of each disc were processed for immunohistochemistry using a type-spec ific, monoclonal antibody raised against human type X collagen. Each intervertebral disc was examined for macroscopic and histomorphological features of disc degeneration. Immunohistochemically, a positive specific type X staining was observed in the hypertrophic zone of the growth plate and only in the interstitial matrix of juvenile (<2 years) nucleus pulposus. In adult discs, type X collagen could be localized in conjunction with advanced disc degeneration and first occurred in the disc matrix (i.e., pericellular region) of a 47-year-old specimen. Positive type X staining of the disc matrix was more frequently found in senile (>70 years) discs with end stages of disc degeneration. This study provides the first evidence for the occurrence of type X collagen in human lumbar intervertebral discs and it appears that type X collagen is re-expressed in late stages of disc degeneration. Accepted: 24 April 1997     

Measurement of surface deformation of soft tissue

A method is described for measuring the surface shape and deformations of soft tissue in three dimensions. The method uses close range stereophotogrammetry to record the three-dimensional locations of miniature optical targets applied to the tissue surface. This has been applied to study of human lumbar intervertebral disc. Measurements of the strain along surface annular fibers have been made under varying loads. In this case the maximum expected errors are about 0.15 mm, which corresponds to a strain of less than 1%. Preliminary findings have differed from predictions made in published mathematical models for the disc in that they show very little strain of the annulus in compression loading, but confirm axial torsional loading as liable to produce mechanical disruption of the disc annulus.     

Reduced nucleus pulposus glycosaminoglycan content alters intervertebral disc dynamic viscoelastic mechanics

The intervertebral disc functions over a range of dynamic loading regimes including axial loads applied across a spectrum of frequencies at varying compressive loads. Biochemical changes occurring in early degeneration, including reduced nucleus pulposus glycosaminoglycan content, may alter disc mechanical behavior and thus may contribute to the progression of degeneration. The objective of this study was to determine disc dynamic viscoelastic properties under several equilibrium loads and loading frequencies, and further, to determine how reduced nucleus glycosaminoglycan content alters dynamic mechanics. We hypothesized that (1) dynamic stiffness would be elevated with increasing equilibrium load and increasing frequency, (2) the disc would behave more elastically at higher frequencies, and finally, (3) dynamic stiffness would be reduced at low equilibrium loads under all frequencies due to nucleus glycosaminoglycan loss. We mechanically tested control and chondroitinase ABC injected rat lumbar motion segments at several equilibrium loads using oscillatory loading at frequencies ranging from 0.05 to 5 Hz. The rat lumbar disc behaved non-linearly with higher dynamic stiffness at elevated compressive loads irrespective of frequency. Phase angle was not affected by equilibrium load, although it decreased as frequency was increased. Reduced glycosaminoglycan decreased dynamic stiffness at low loads but not at high equilibrium loads and led to increased phase angle at all loads and frequencies. The findings of this study demonstrate the effect of equilibrium load and loading frequencies on dynamic disc mechanics and indicate possible mechanical mechanisms through which disc degeneration can progress.     

Lumbar muscularity and its relationship with age, occupation and low back pain.

This paper considers an internal standard of lumbar muscularity. The cross-sectional areas (Acs) of the intervertebral disc and paraspinal muscles were measured in 147 working men from an axial magnetic resonance image passing through the L3-4 disc. Lumbar muscularity was expressed by two ratios; the ratio between the Acs of the right psoas and the Acs of the intervertebral disc (P:disc), and the ratio between the combined Acs values of the right erector spinae and quadratus lumborum and the Acs of the disc (ESQL:disc). When the subjects were divided into two age groups (76 aged 20-30 years and 71 aged 31-58 years) lumbar muscularity was found to be significantly greater (P less than 0.001) in the younger age group (P:disc = 0.8, SD 0.2; ESQL:disc = 2.0, SD 0.3) than in the older age group (P:disc = 0.7, SD 0.2; ESQL:disc = 1.8, SD 0.3). Lumbar muscularity was not significantly affected by occupation or by a history of low back pain.     

Numerical analysis of the influence of nucleus pulposus removal on the biomechanical behavior of a lumbar motion segment

Nucleus replacement was deemed to have therapeutic potential for patients with intervertebral disc herniation. However, whether a patient would benefit from nucleus replacement is technically unclear. This study aimed to investigate the influence of nucleus pulposus (NP) removal on the biomechanical behavior of a lumbar motion segment and to further explore a computational method of biomechanical characteristics of NP removal, which can evaluate the mechanical stability of pulposus replacement. We, respectively, reconstructed three types of models for a mildly herniated disc and three types of models for a severely herniated disc based on a L4–L5 segment finite element model with computed tomography image data from a healthy adult. First, the NP was removed from the herniated disc models, and the biomechanical behavior of NP removal was simulated. Second, the NP cavities were filled with an experimental material (Poisson's ratio = 0.3; elastic modulus = 3 MPa), and the biomechanical behavior of pulposus replacement was simulated. The simulations were carried out under the five loadings of axial compression, flexion, lateral bending, extension, and axial rotation. The changes of the four biomechanical characteristics, i.e. the rotation degree, the maximum stress in the annulus fibrosus (AF), joint facet contact forces, and the maximum disc deformation, were computed for all models. Experimental results showed that the rotation range, the maximum AF stress, and joint facet contact forces increased, and the maximum disc deformation decreased after NP removal, while they changed in the opposite way after the nucleus cavities were filled with the experimental material.     

The effect of passive vertebral rotation on pressure in the nucleus pulposus

To study the immediate effects of axial rotation on the intervertebral disc, six pig cadaver lumbar functional spinal units were exposed to rotations of up to 2 degrees, while disc height and intradiscal pressure were measured. The results showed that rotary movements are capable of causing an immediate increase in disc height and drop in nucleus pressure. However, the long-term effects were opposite in direction.     

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

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 low- and 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.     

一种新型大鼠腰椎间盘突出症动物模型的建立

目的建立一种大鼠腰椎间盘突出症的动物模型。方法采用自体髓核移植至背根神经节＋铬制肠线环扎神经根的方法,建立根性神经痛模型,观察背根神经节的组织学改变及超微结构改变,用Von Frey针丝和RTX-1型热痛测试仪检测动物的痛觉行为改变。结果该方法可诱导出明显的机械刺激痛觉超敏与热刺激痛觉过敏,术后1周时最为明显,术后3周时仍有较明显的神经行为异常;术后1周时背根节出现明显的充血水肿,而术后3周以脱髓样改变和纤维细胞增生为主。结论自体髓核移植＋铬制肠线环扎神经根可较好地引起根性神经痛的发生,可作为研究椎间盘突出症的动物模型。     

Streaming potential of human lumbar anulus fibrosus is anisotropic and affected by disc degeneration.

The streaming potential responses of non-degenerate and degenerate human anulus fibrosus were measured in a one-dimensional permeation configuration under static and dynamic loading conditions. The goal of this study was to investigate the influence of the changes in tissue structure and composition on the electrokinetic behavior of intervertebral disc tissues. It was found that the static streaming potential of the anulus fibrosus depended on the degenerative grade of the discs (p = 0.0001) and on the specimen orientation in which the fluid flows (p = 0.0001). For a statically applied pressure of 0.07 MPa, the ratio of streaming potential to applied pressure ranged from 5.3 to 6.9 mV/MPa and was largest for Grade I tissue with axial orientation and lowest for Grade III tissue with circumferential orientation. The dynamic streaming potential responses of anulus fibrosus were sensitive to the degeneration of the disc: the total harmonic distortion factor increased by 108%, from 3.92 +/- 0.66% (mean +/- SD) for Grade I specimens to 8.15 +/- 3.05% for Grades II and III specimens. The alteration of streaming potential reflects the changes in tissue composition and structure with degeneration. To our knowledge, this is the first reported data for the streaming potential of human intervertebral disc tissues. Knowledge of the streaming potential response of the intervertebral disc provides an understanding of potentially important signal transduction mechanisms in the disc and of the etiology of intervertebral disc degeneration.     

Moderately degenerated lumbar motion segments: Are they truly unstable?

The two main load bearing tissues of the intervertebral disc are the nucleus pulposus and the annulus fibrosus. Both tissues are composed of the same basic components, but differ in their organization and relative amounts. With degeneration, the clear distinction between the two tissues disappears. The changes in biochemical content lead to changes in mechanical behaviour of the intervertebral disc. The aim of the current study was to investigate if well-documented moderate degeneration at the biochemical and fibre structure level leads to instability of the lumbar spine. By taking into account biochemical and ultrastructural changes to the extracellular matrix of degenerating discs, a set of constitutive material parameters were determined that described the individual tissue behaviour. These tissue biomechanical models were then used to simulate dynamic behaviour of the degenerated spinal motion segment, which showed instability in axial rotation, while a stabilizing effect in the other two principle bending directions. When a shear load was applied to the degenerated spinal motion segment, no sign of instability was found. This study found that reported changes to the nucleus pulposus and annulus fibrosus matrix during moderate degeneration lead to a more stable spinal motion segment and that such biomechanical considerations should be incorporated into the general pathophysiological understanding of disc degeneration and how its progress could affect low back pain and its treatments thereof.     

正常椎间盘胶原的研究

腰椎间盘突出症是引起腰腿痛常见的原因。胶原作为椎间盘结构的主要成分,构成椎间盘的纤维框架,其类型与分布直接决定着椎间盘结构的强度和功能的稳定。本文利用溴化氰消化椎间盘胶原产生多肽,借助于梯度层析。SDS-PAGE及光密度定量扫描等对正常人椎间盘胶原进行了研究。结果表明:正常人椎间盘含Ⅰ型及Ⅱ型两种胶原,它们的分布呈明显而特征性的移行性变化:纤维环外层边缘以Ⅰ型胶原为主(83％),由外向内Ⅰ型胶原逐渐移行为Ⅱ型胶原,靠近髓核处以Ⅱ型胶原为主(72％);髓核中心含有Ⅱ型胶原。此为椎间盘的一个结构特性,以满足椎间盘的特殊功能的需要。     

Lumbar spine angles and intervertebral disc characteristics with end-range positions in three planes of motion in healthy people using upright MRI

Understanding changes in lumbar spine (LS) angles and intervertebral disc (IVD) behavior in end-range positions in healthy subjects can provide a basis for developing more specific LS models and comparing people with spine pathology. The purposes of this study are to quantify 3D LS angles and changes in IVD characteristics with end-range positions in 3 planes of motion using upright MRI in healthy people, and to determine which intervertebral segments contribute most in each plane of movement. Thirteen people (average age = 24.4 years, range 18–51 years; 9 females; BMI = 22.4 ± 1.8 kg/m²) with no history of low back pain were scanned in an upright MRI in standing, sitting flexion, sitting axial rotation (left, right), prone on elbows, prone extension, and standing lateral bending (left, right). Global and local intervertebral LS angles were measured. Anterior-posterior length of the IVD and location of the nucleus pulposus was measured. For the sagittal plane, lower LS segments contribute most to change in position, and the location of the nucleus pulposus migrated from a more posterior position in sitting flexion to a more anterior position in end-range extension. For lateral bending, the upper LS contributes most to end-range positions. Small degrees of intervertebral rotation (1–2°) across all levels were observed for axial plane positions. There were no systematic changes in IVD characteristics for axial or coronal plane positions.     

人工椎间盘的拓扑优化探讨--正压条件下人工椎间盘有限元优化分析

目的：研究人工椎间盘力学结构特点,探讨改进设计优化结构的依据。方法：在用有限元法进行正压下力学分析的基础上,对模型不同构件进行拓扑优化分析。结果：获得正压下假体模型主应力,作用力及支座反力的特点;指明拓扑优化的几何区域。结论：人工椎间盘的设计改进要在相关力学分析的基础上进行;通过优化分析既指明了假体结构上的重要区域,也显示出模型不同空间位置的可优化程度,为改进设计提供初步参考依据。有限元优化设计是假体研究,设计中经济有效的辅助方法。     

Numerical exploration of the combined effect of nutrient supply,tissue condition and deformation in the intervertebral disc

Novel strategies to heal discogenic low back pain could highly benefit from comprehensive biophysical studies that consider both mechanical and biological factors involved in intervertebral disc degeneration. A decrease in nutrient availability at the bone–disc interface has been indicated as a relevant risk factor and as a possible initiator of cell death processes. Mechanical behaviour of both healthy and degenerated discs could highly interact with cell death in these compromised situations. In the present study, a mechano-transport finite element model was used to investigate the nature of mechanical effects on cell death processes via load-induced metabolic transport variations. Cycles of static sustained compression were chosen to simulate daily human activity. Healthy and degenerated cases were simulated as well as a reduced supply of solutes and an increase in solute exchange area at the bone–disc interface. Results showed that a reduction in metabolite concentrations at the bone–disc boundaries induced cell death, even when the increased exchange area was simulated. Slight local mechanical enhancements of glucose in the disc centre were capable of decelerating cell death but occurred only with healthy mechanical properties. However, mechanical deformations were responsible for a worsening in terms of cell death in the inner annulus, a disadvantaged zone far from the boundary supply with both an increased cell demand and a strain-dependent decrease of diffusivity. Such adverse mechanical effects were more accentuated when degenerative properties were simulated. Overall, this study paves the way for the use of biophysical models for a more integrated understanding of intervertebral disc pathophysiology.     

Statistical factorial analysis on the poroelastic material properties sensitivity of the lumbar intervertebral disc under compression,flexion and axial rotation

A statistical factorial analysis approach was conducted on a poroelastic finite element model of a lumbar intervertebral disc to analyse the influence of six material parameters (permeabilities of annulus, nucleus, trabecular vertebral bone, cartilage endplate and Young's moduli of annulus and nucleus) on the displacement, fluid pore pressure and velocity fields. Three different loading modes were investigated: compression, flexion and axial rotation. Parameters were varied considering low and high levels in agreement with values found in the literature for both healthy and degenerated lumbar discs. Results indicated that annulus stiffness and cartilage endplate permeability have a strong effect on the overall fluid- and solid-phase responses in all loading conditions studied. Nucleus stiffness showed its main relevance in compression while annulus permeability influenced mainly the annular pressure field. This study confirms the permeability's central role in biphasic modelling and highlights for the lumbar disc which experiments of material property characterization should be performed. Moreover, such sensitivity study gives important guidelines in poroelastic material modelling and finite element disc validation.     

The micromechanical role of the annulus fibrosus components under physiological loading of the lumbar spine

To date, studies that have investigated the kinematics of spinal motion segments have largely focused on the contributions that the spinal ligaments play in the resultant motion patterns. However, the specific roles played by intervertebral disk components, in particular the annulus fibrosus, with respect to global motion is not well understood in spite of the relatively large literature base with respect to the local ex vivo mechanical properties of the tissue. The primary objective of this study was to implement the nonlinear and orthotropic mechanical behavior of the annulus fibrosus in a finite element model of an L4/L5 functional spinal unit in the form of a strain energy potential where the individual mechanical contributions of the ground substance and fibers were explicitly defined. The model was validated biomechanically under pure moment loading to ensure that the individual role of each soft tissue structure during load bearing was consistent throughout the physiologically relevant loading range. The fibrous network of the annulus was found to play critical roles in limiting the magnitude of the neutral zone and determining the stiffness of the elastic zone. Under flexion, lateral bending, and axial rotation, the collagen fibers were observed to bear the majority of the load applied to the annulus fibrosus, especially in radially peripheral regions where disk bulging occurred. For the first time, our data explicitly demonstrate that the exact fiber recruitment sequence is critically important for establishing the range of motion and neutral zone magnitudes of lumbar spinal motion segments.     

What have we learned from finite element model studies of lumbar intervertebral discs in the past four decades?

Finite element analysis is a powerful tool routinely used to study complex biological systems. For the last four decades, the lumbar intervertebral disc has been the focus of many such investigations. To understand the disc functional biomechanics, a precise knowledge of the disc mechanical, structural and biochemical environments at the microscopic and macroscopic levels is essential. In response to this need, finite element model studies have proven themselves as reliable and robust tools when combined with in vitro and in vivo measurements.     

Periostin is expressed by cells of the human and sand rat intervertebral discs

Abstract

Periostin, a matricellular protein in the fasciclin family, is expressed in tissues subjected to constant mechanical stress. Periostin modulates cell-to-extracellular matrix interactions and can bind to collagen, fibronectin, tenascin-C and several integrins. Our objective was to evaluate whether periostin is expressed in the human intervertebral disc. Immunohistochemical localization of periostin was carried out in tissue of human lumbar discs and lumbar discs of the sand rat (Psammomys obesus). Human discs also were examined for periostin gene expression. Immunohistochemical localization demonstrated periostin in the cytoplasm of annulus and nucleus cells, and occasionally in the surrounding pericellular and interterritorial extracellular matrix. Periostin distribution in the human disc was distinctive. Outer annulus contained the highest proportion of periostin-positive cells (88.8%), whereas inner annulus contained only 61.4%. The nucleus pulposus contained the fewest periostin-positive cells (18.5%). There was a significant negative correlation between the percentage of cells positive for periostin in the inner annulus and subject age. Periostin gene expression in the human disc also was confirmed using molecular microarray analysis. Because work by others has shown that periostin plays an important role in the biomechanical properties of other connective tissues (skin, tendon, heart valves), future research is needed to elucidate the role of periostin in disc, loading, aging and degeneration.