Finite-element simulation of changes in the fluid content of human lumbar discs. Mechanical and clinical implications.

The effect of alteration in the nucleus fluid content on the mechanics of a lumbar motion segment was analyzed by a finite-element model. Various combined loads were applied on the lumbar segment and were then kept constant while the disc-confined fluid was changed incrementally to a maximum of 12% gain or loss in its original volume. Change in the nucleus volume directly affected the intradiscal pressure. Loss of nucleus fluid content increased the contact forces on the facets and diminished tensile forces in the anulus fiber layers. The inner anulus layers were more affected than the outer ones. Reverse trends were computed when the nucleus fluid content was increased. Except in combined extension and compression loading, fluid gain increased the segmental stiffness while the overall stiffness lessened with loss of fluid content. Loss of the nucleus fluid caused inward bulge at the inner anulus layers and altered the stress distribution in the vertebral bodies. The nucleus material normally carries a portion of the applied compression and stresses and supports the surrounding anulus layers. A loss in the nucleus-confined fluid disrupted the normal mechanical function of the nucleus, whereby disc anulus layers were predisposed to lateral instability and disintegration, and hence to further degeneration; facets were subjected to significant additional loads; and vertebral bodies underwent a markedly different stress distribution.     

Regional variations in the compressive properties of lumbar vertebral trabeculae. Effects of disc degeneration

The compressive mechanical properties of human lumbar vertebral trabeculae were examined on the basis of anatomic origin, bone density, and intervertebral disc properties. Trabecular bone compressive strength and stiffness increased with increasing bone density, the latter proportional to strength and stiffness to the one-half power. Regional variations within each segment were found, the most prevalent differences occurring in regions of bone overlying the disc nucleus in comparison with bone overlying the disc anulus. For normal discs, the ratio of strength of bone overlying the disc nucleus to bone overlying the disc anulus was 1.25, decreasing to 1.0 for moderately degenerated discs. These results suggest that an interdependency of trabecular bone properties and intervertebral disc properties may exist.     

Effects of anulus fibrosus and experimentally degenerated nucleus pulposus on nerve root conduction velocity: relevance of previous experimental investigations using normal nucleus pulposus

STUDY DESIGN: Nerve conduction velocity was measured in the pig cauda equina after local application of anulus fibrosus or in vitro/postmortem degenerated nucleus pulposus from the same pig. OBJECTIVES: To analyze the effects of anulus fibrosus and degenerated nucleus pulposus on nerve conduction velocity. SUMMARY OF BACKGROUND DATA: Previous studies on nucleus pulposus-induced effects on nerve roots have used normal, nondegenerated nucleus pulposus. Because both anulus fibrosus and degenerated nucleus pulposus are commonly seen in the clinical situation of disc herniation, the value of the previous work could be questioned. METHODS: Anulus fibrosus and nucleus pulposus were harvested using a retroperitoneal approach. The nucleus pulposus was degenerated artificially either by addition of sodium lactate with HCl added to form a pH of either 6.0 or 3.5 (in vitro degeneration), or by storing the nucleus pulposus at 4 C until a pH of 6.0 (postmortem degeneration) was reached. After epidural application, the nerve conduction velocity was determined at 7 days (anulus fibrosus) or 3 days (degenerated nucleus pulposus). RESULTS: Application of anulus fibrosus did not induce any reduction of nerve conduction velocity. In vitro and postmortem degenerated nucleus pulposus induced a reduction of nerve conduction velocity similar to that of normal nucleus pulposus. CONCLUSIONS: Although only nerve function and not pain was assessed, it seems likely that previous experiments using normal nucleus pulposus may be relevant for evaluating the pathophysiologic mechanisms behind the nucleus pulposus-induced nerve root injury, also in a clinical perspective.     

退变椎体周边关节软骨产生碱性磷酸酶与骨赘形成的关系

目的：研究椎体骨赘形成的机理。方法：通过切除免颈棘上韧带及棘间和分离颈椎后旁两侧肌肉引起动物颈椎力学上的失衡,经３个月的时间的发展而造成免颈椎间盘退变模型。用生物化学方法分别测定每个动物颈椎间盘纤维环和髓核、椎体关系软骨、周边关节软碱性磷酸酶性结果：颈椎间盘退变动物椎体周边关节软骨中碱性磷酸酶活性明显升高。结论：研究结果在生物化学上支持椎体骨赘来自于周边关节软骨增殖、化生、钙化和骨化的组织学观察。     

In vitro torsion-induced stress distribution changes in porcine intervertebral discs.

STUDY DESIGN: A cadaveric porcine spine motion segment experiment was conducted. OBJECTIVE: To test the hypothesis that small vertebral rotations cause increased stress in the anulus while decreasing stress in the nucleus through stiffening of the anulus. SUMMARY OF BACKGROUND DATA: Stress profiles of the intervertebral disc reportedly depend on degeneration grade and external loading. Increased stress in the anulus was found during asymmetric loading. In addition, depressurization of the nucleus combined with an instantaneous disc height increase was found when small (<2 degrees ) axial vertebral rotations were applied. METHODS: Seven lumbar porcine cadaveric motion segments consisting of two vertebrae and the intervening disc with ligaments were loaded in the neutral position with 340 N of compression. Stress profiles were obtained in the neutral position, then after 0.5 degrees and 1 degrees axial rotation of the bottom vertebral body. The distribution of compressive stress in the disc matrix was measured by pulling a miniature pressure transducer through the disc along a straight path in the midfrontal plane. Stress profiles were measured in vertical (0 degrees ) and horizontal (90 degrees ) orientation. RESULTS: Deformation of the anulus by small axial rotations of the lower vertebra instantaneously decreased the horizontally and vertically measured stress in the nucleus while increasing stress in the anulus. A 1-hour period of creep loading decreased the stresses in the nucleus and the anulus 20% to 30%, depending on the orientation, but the effect of an increasing stress in the anular region after axial rotation persisted. CONCLUSIONS: The compressive Young's modulus of the composite anulus tissue increases instantaneously when small axial rotations are applied to porcine spine motion segments. This is accompanied by decreased stress in the nucleus pulposus, increased stress in the anulus fibrosus, changes in the stress profile superimposed on and independent of prolonged viscoelastic creep and dehydration, and changes in stress distribution independent of horizontal and vertical orientation.     

Influence of disc degeneration on mechanism of thoracolumbar burst fractures.

In order to clarify the pathomechanism of thoracolumbar burst fractures and to evaluate the influence of disc degeneration and bone mineral density, a biomechanical study was performed using cadaveric spines. Eleven motion segments of thoracolumbar spines from human cadavers were compressed vertically until a fracture occurred. In addition, bone mineral density and degree of disc degeneration were determined for each specimen. Compression of 7 of 11 specimens resulted in the typical burst fracture characterized by retropulsion of a bony fragment into the spinal canal and an increase of the interpedicular distance. All seven specimens showed disruptions of the middle end plate and disc materials in the vertebral body. The fracture line was located between the middle of the end plate and the middle of the posterior wall cortex. No burst fractures were seen in the specimens with severely degenerated discs and osteoporosis. In order to confirm the stress state in a vertebra that induces the burst fracture, finite element analysis of one motion segment was also carried out under the same mechanical conditions as the experiments in this study. As a result of calculation for the healthy disc, the highest stresses under axial compression were concentrated in the following areas: the middle of the end plate, the cancellous bone under the nucleus pulposus, and the middle of the posterior wall cortex. This implies that the above regions are more vulnerable to vertical compressive load. In the analysis of specimens with severely degenerated discs, stresses were very low at the end plate and cancellous bone under the nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanical initiation of intervertebral disc degeneration

STUDY DESIGN: Mechanical testing of cadaveric lumbar motion segments. OBJECTIVES: To test the hypothesis that minor damage to a vertebral body can lead to progressive disruption of the adjacent intervertebral disc. SUMMARY OF BACKGROUND DATA: Disc degeneration involves gross structural disruption as well as cell-mediated changes in matrix composition, but there is little evidence concerning which comes first. Comparatively minor damage to a vertebral body is known to decompress the adjacent discs, and this may adversely affect both structure and cell function in the disc. METHODS: In this study, 38 cadaveric lumbar motion segments (mean age, 51 years) were subjected to complex mechanical loading to simulate typical activities in vivo while the distribution of compressive stress in the disc matrix was measured using a pressure transducer mounted in a needle 1.3 mm in diameter. "Stress profiles" were repeated after a controlled compressive overload injury had reduced motion segment height by approximately 1%. Moderate repetitive loading, appropriate for the simulation of light manual labor, then was applied to the damaged specimens for approximately 4 hours, and stress profilometry was repeated a third time. Discs then were sectioned and photographed. RESULTS: Endplate damage reduced pressure in the adjacent nucleus pulposus by 25% +/- 27% and generated peaks of compressive stress in the anulus, usually posteriorly to the nucleus. Discs 50 to 70 years of age were affected the most. Repetitive loading further decompressed the nucleus and intensified stress concentrations in the anulus, especially in simulated lordotic postures. Sagittal plane sections of 15 of the discs showed an inwardly collapsing anulus in 9 discs, extreme outward bulging of the anulus in 11 discs, and complete radial fissures in 2 discs, 1 of which allowed posterior migration of nucleus pulposus. Comparisons with the results from tissue culture experiments indicated that the observed changes in matrix compressive stress would inhibit disc cell metabolism throughout the disc, and could lead to progressive deterioration of the matrix. CONCLUSIONS: Minor damage to a vertebral body endplate leads to progressive structural changes in the adjacent intervertebral discs.     

Reduction in segmental flexibility because of disc degeneration is accompanied by higher changes in facet loads than changes in disc pressure: a poroelastic C5–C6 finite element investigation

Background contextNerve fiber growth inside the degenerative intervertebral discs and facets is thought to be a source of pain, although there may be several other pathological and clinical reasons for the neck pain. It, however, remains difficult to decipher how much disc and facet joints contribute to overall degenerative segmental responses. Although the biomechanical effects of disc degeneration (DD) on segmental flexibility and posterior facets have been reported in the lumbar spine, a clear understanding of the pathways of degenerative progression is still lacking in the cervical spine.PurposeTo test the hypothesis that after an occurrence of degenerative disease in a cervical disc, changes in the facet loads will be higher than changes in the disc pressure.Study designTo understand the biomechanical relationships between segmental flexibility, disc pressure, and facet loads when the C5–C6 disc degenerates.MethodsA poroelastic, three-dimensional finite element (FE) model of a normal C5–C6 segment was developed and validated. Two degenerated disc models (moderate and severe) were built from the normal disc model. Biomechanical responses of the three FE models (normal, moderate, and severe) were further studied under diurnal compression (at the end of the daytime activity period) and moment loads (at the end of 5 seconds) in terms of disc height loss, angular motions, disc pressure, and facet loads (average of right and left facets).ResultsDisc deformation under compression and segmental rotational motions under moment loads for the normal disc model agreed well with the corresponding in vivo studies. A decrease in segmental flexibility because of DD is accompanied by a decrease in disc pressure and an increase in facet loads. Biomechanical effects of degenerative disc changes are least in flexion. Segmental flexibility changes are higher in extension, whereas changes in disc pressure and facet loads are higher in lateral bending and axial rotation, respectively.ConclusionsThe results of the present study confirmed the hypothesis of higher changes in facet loads than in disc pressure, suggesting posterior facets are more affected than discs because of a decrease in degenerative segmental flexibility. Therefore, a degenerated disc may increase the risk of overloading the posterior facet joints. It should be clearly noted that only after degeneration simulation in the disc, we recorded the biomechanical responses of the facets and disc. Therefore, our hypothesis does not suggest that facet joint osteoarthritis may occur before degeneration in the disc. Future cervical spine–based experiments are warranted to verify the conclusions presented in this study.     

Localization of cathepsins D, K, and L in degenerated human intervertebral discs.

STUDY DESIGN: Localization of cathepsins D, K, and L in degenerated intervertebral discs was examined by immunohistochemistry. OBJECTIVES: To determine the involvement of cathepsins in the pathomechanism of intervertebral disc degeneration by monitoring the immunolocalization of cathepsins in degenerated intervertebral disc tissue. SUMMARY OF BACKGROUND DATA: Cathepsins D, K, and L are enzymes that contribute to the matrix destruction seen in the articular cartilage affected by osteoarthritis and rheumatoid arthritis. However, little is known about the contribution of these cathepsins to intervertebral disc degeneration. METHODS: Paraffin-embedded sections of degenerated intervertebral disc tissue collected at the time of surgery (13 discs from 12 patients) were immunohistochemically stained with antibodies for cathepsins D, K, and L. For further characterization of the stained cells, immunohistochemical detection of CD68 and TRAP staining were performed. RESULTS: Hematoxylin and eosin staining revealed obvious signs of degeneration in all sections. Cathepsins D and L were immunolocalized in disc fibrochondrocytes at various sites exhibiting degeneration. Cathepsins K were found in tartrate-resistant acid phosphatase-positive multinucleated cells, in particular near the cleft within the cartilaginous endplate. However, few cells were positive for these cathepsins in anulus fibrosus that maintained the lamellar structure of collagen fibers. CONCLUSIONS: Marked expression of cathepsins D and L was observed at the site of degeneration. Cathepsins D and K localized in tartrate-resistant acid phosphatase-positive multinucleated cells existed at the cleft between the cartilaginous endplate and vertebral body. The site-specific localization of these cathepsins suggests the association of these proteinases with endplate separation and disorganization of the anulus fibrosus in degenerative spinal disorders.     

Contribution of facet joints,axial compression,and composition to human lumbar disc torsion mechanics

Stresses applied to the spinal column are distributed between the intervertebral disc and facet joints. Structural and compositional changes alter stress distributions within the disc and between the disc and facet joints. These changes influence the mechanical properties of the disc joint, including its stiffness, range of motion, and energy absorption under quasi‐static and dynamic loads. There have been few studies evaluating the role of facet joints in torsion. Furthermore, the relationship between biochemical composition and torsion mechanics is not well understood. Therefore, the first objective of this study was to investigate the role of facet joints in torsion mechanics of healthy and degenerated human lumbar discs under a wide range of compressive preloads. To achieve this, each disc was tested under four different compressive preloads (300–1200 N) with and without facet joints. The second objective was to develop a quantitative structure‐function relationship between tissue composition and torsion mechanics. Facet joints have a significant contribution to disc torsional stiffness (～60%) and viscoelasticity, regardless of the magnitude of axial compression. The findings from this study demonstrate that annulus fibrosus GAG content plays an important role in disc torsion mechanics. A decrease in GAG content with degeneration reduced torsion mechanics by more than an order of magnitude, while collagen content did not significantly influence disc torsion mechanics. The biochemical‐mechanical and compression‐torsion relationships reported in this study allow for better comparison between studies that use discs of varying levels of degeneration or testing protocols and provide important design criteria for biological repair strategies. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2266–2273, 2018.

     

In vitro hyperextension injuries in the human cadaveric cervical spine.

To investigate the relationship between the type of hyperextension injuries and the conditions producing them, nine cervical specimens (occiput to T1) were loaded to failure in tension at a fixed extension angle of 30 degrees. Under these loading conditions, specimens failed at average tensile loads and extension moments of 499 +/- 148 (SD) N and 4.0 +/- 3.1 Nm, respectively. Failure occurred at an average tensile displacement of 18.8 +/- 7.7 mm. The anterior longitudinal ligament ruptured and the intervertebral disc failed in at least one level in all specimens. In four specimens, the disc failed at an additional level, leaving the anterior longitudinal ligament intact at that site. With one exception, all injuries occurred in the lower cervical spine (C5-C6 and C6-C7), the region most often injured in vivo. The location of the injuries was associated with the degree of degeneration of the facet joints and the discs. The discs of the lower cervical spine were significantly more degenerated than those at the C2-C3 level. In addition, the degree of disc degeneration in the noninjured discs was significantly less than in the injured discs. These data help quantify the threshold of injury and the patterns of tissue damage resulting from hypertension loading of the cervical spine.     

颈椎椎间盘退变对终板结构生物力学特性的影响

目的研究颈椎椎间盘对终板结构生物力学特性的影响。方法50节颈椎标本,采用Nachemson椎间盘分级标准将标本分为4组,正常组(n=22)、Ⅰ度退变组(n=10)、Ⅱ度退变组(n=9)、Ⅲ度退变组(n=9),对每一终板平面上20个特定的测试点进行压缩实验,直径2mm的半球形压头以003mm/s的速度垂直于终板平面下压2mm,由所得的力─位移曲线计算出最大压缩力及刚度,采用单因素方差分析、析因分析、SNK检验及相关分析对实验数据进行统计学分析。结果颈椎椎间盘退变可导致颈椎终板最大压缩力及刚度的显著性减小(P<001),且存在负相关关系(分别为rs=-0429,P<0001;rs=-0244,P<0001);上终板随着椎间盘退变的加重终板平面中央承力逐渐变弱,外周承力逐渐增强,下终板的力学分布无明显改变。结论颈椎椎间盘退变是影响终板结构生物力学特性的重要因素,在进行颈椎前路融合术时应警惕由于椎间盘退变引起的“植入物沉陷”。     

Influence prediction of injury and vibration on adjacent components of spine using finite element methods

OBJECTIVES: A three-dimensional finite element (FE) model of the lumbar spine L3-L5 segment, the ligaments of which were assumed to be nonlinear materials, was established based on the actual vertebra geometry to investigate the influence of the injury lumbar spine on its adjacent components on the condition of whole-body vibration. Several injury conditions of the spine components were assumed, such as facetectomy, nucleotomy, and removal of bony posterior elements. METHODS: The dynamic FE analyses were carried out for those FE conditions under cyclic compression loads at the frequencies of 5 and 10 Hz. Then a comparison between the dynamic results and the static results was conducted to analyze the influence of both the nucleus injury and the facet joint injury on the adjacent intervertebral discs. RESULTS AND CONCLUSIONS: The results indicate that the lumbar spine exhibits not only vertical vibration but also the flexion--extension motion during vibration. The denucleation will cause high stress and large disc bulge on the disc annulus under vibration. The facet joints of lumbar spine can limit the motion amplitude of flexion-extension and protect both the posterior regions and the posterolateral regions of disc annulus from large strain and stress during vibration. The facet joint removal will increase the stress of disc annulus by around 15% at the posterior region for the conditions of nucleotomy or no vibration. The stress of annulus circumference is higher at the posterolateral region than that of other regions of annulus circumference, and the facet joint removal may exacerbate the intervertebral disc degeneration on the condition of whole-body vibration.     

Pathology and possible mechanisms of nervous system response to disc degeneration

Degeneration of the intervertebral disc is clinically considered to be an important source of pain in patients with low-back pain. Disc deterioration and/or degeneration may influence the nervous system by stimulation of nociceptors in the anulus fibrosus, causing nociceptive pain that is often referred to as discogenic pain. The stimulation of the nociceptors may be of mechanical or inflammatory origin. Deterioration of a disc with loss of normal structure and weight-bearing properties may lead to abnormal motions that cause mechanical stimulation. This theory is supported by the fact that patients commonly experience an increase in pain with weight-bearing and certain movements. In addition, an ingrowth of vessels and nerve fibers into deeper layers of the anulus fibrosus has been observed in degenerated discs. A large number of inflammatory and signaling substances, such as tumor necrosis factor and interleukins (interleukin-1beta, interleukin-6, and interleukin-8), may also play a role in the development of back pain. Independent of stimulus of the nociceptors, the pain impulses are conducted through myelinated A delta fibers and unmyelinated C fibers to the dorsal root ganglion and continue by way of the spinothalamic tract to the thalamus and the somatosensory cortex. In response to stimulation of the nociceptors in the disc, the somatosensory system may increase its sensitivity, resulting in a nonfunctional response; that is, normally innocuous stimuli may generate an amplified response (peripheral sensitization). When disc degeneration leads to a disc herniation, the adjacent nervous system structures, such as the nerve roots or the dorsal root ganglion, can be affected, causing neuropathic pain of mechanical or biochemical origin. Disc deterioration also influences other spinal structures, such as facet joints, ligaments, and muscles, which can also become pain generators. Thus, disc degeneration may be responsible for the development of chronic low-back pain without being the actual pain focus. Both nociceptive and neuropathic pain can be modulated at higher centers, both at the spinal and the supraspinal levels (central sensitization). The altered magnitude of perceived pain is often referred to as neural plasticity and is considered to play a critical role in the evolution of chronic pain. Together with the complexity of the nervous system and pain modulation mechanisms, psychological aspects may also play a role in the response of the nervous system in patients with chronic low-back pain caused by disc degeneration.     

Effects of aging and spinal degeneration on mechanical properties of lumbar supraspinous and interspinous ligaments.

BACKGROUND CONTEXT: The effects of aging and spinal degeneration on the mechanical properties of spinal ligaments are still unknown, although there have been several studies demonstrating those of normal spinal ligaments. PURPOSE: To investigate the mechanical properties of the human posterior spinal ligaments in human lumbar spine, and their relation to age and spinal degeneration parameters. STUDY DESIGN/SETTING: Destructive uniaxial tensile tests were performed on the human supraspinous and interspinous ligaments at L4-5 level. Their mechanical properties were compared with age and spinal degeneration using several imaging modalities. PATIENT SAMPLE: Twenty-four patients with lumbar degenerative diseases on whom posterior surgeries were performed, with the age ranging from 18 to 85 years. OUTCOME MEASURES: The ultimate load and elastic stiffness as structural properties, the degree of disc degeneration, range of segmental motion, the disc height, disc space narrowing ratio and degree of facet degeneration as the parameters of spinal degeneration. METHODS: Twenty-four supraspinous and interspinous ligaments at the L4-5 level were obtained from posterior surgeries of patients with lumbar degenerative disease. The mechanical tests of bone-ligament-bone complexes were performed in a uniaxial tensile fashion with a specially designed clamp device. The ultimate load and elastic stiffness were calculated as structural properties. The degree of disc degeneration, range of segmental motion, the disc height, disc space narrowing ratio and degree of facet degeneration were examined by using radiographs, computed tomography and magnetic resonance imaging. RESULTS: The average and SD value of ultimate load, elastic stiffness, tensile strength and elastic modulus were 203+/-102.9 N, 60.6+/-36.7 N/mm, 1.2+/-0.6 Mpa and 3.3+/-2.1 Mpa, respectively. A significant negative correlation was found between age and tensile strength (p= 0.02). The specimens with facet degeneration showed lower values in tensile strength and elastic modulus than those without facet degeneration (p<0.04). However, no correlation was found between disc-related parameters and tensile strength. CONCLUSIONS: The mechanical strength of human lumbar posterior spinal ligaments decreases with age and facet degeneration, particularly in the ligament substance.     

Peak stresses observed in the posterior lateral anulus

STUDY DESIGN: The stress distributions within cadaveric lumbar intervertebral discs were measured for a range of loading conditions. OBJECTIVES: To examine the distribution of stress across the area of the intervertebral disc and to compare regional variations in peak stress during compression loading with various flexion angles. SUMMARY OF BACKGROUND DATA: The rate of disc degeneration and the occurrence of low back disorders increase with higher mechanical loading of the spine. The largest peak stresses occur in the anulus. METHODS: Human lumbar L2--L3 and L4--L5 cadaver functional spinal units were obtained and tested. The distribution of disc stress was measured using a pressure probe with loads applied, pure compression and compression with 5 degrees of either flexion or extension. RESULTS: Stress profiles were recorded across the intervertebral disc at a compressive force of 1000 N and each of the three flexion-extension angles. The highest values (2.99 +/- 1.31 MPa) were measured during extension-compression lateral to the midline of the disc in the posterior anulus. The pressure in the nucleus was relatively unchanged by flexion angle remaining about 1.00 MPa for a 1000-N compression. CONCLUSIONS: Pressure measurements of the cadaveric nucleus have been used to validate models of lumbar spine loading and to evaluate the risk of low back injury and disc herniation. Previous observations limited to midsagittal measurements of the nucleus did not identify the regions of highest stress. The highest values observed here within the posterolateral anulus correspond to common sites of disc degeneration and herniation.     

Basic science of spinal degeneration

This article summarizes recent advances in our understanding of spinal pathology and pain. Degeneration appears to start in the intervertebral discs, often before age 20 years, and can be distinguished from ‘normal’ ageing by the presence of physical disruption, typically in the form of annulus fissures, prolapse or endplate fracture. Disruption is ultimately mechanical, but frustrated attempts by a small population of disc cells to heal a large avascular matrix give rise to the typical biological features of disc degeneration. Genetic inheritance and ageing are important risk factors for disc degeneration because they can weaken the disc matrix, and hinder repair processes. Discogenic pain appears to arise from the disc periphery as a result of in-growing nerves being sensitized by soluble factors from activated disc and blood cells. A degenerated disc loses pressure in the nucleus and bulges radially outwards, like a flat tyre. This often leads to a transient segmental instability, which can be reversed by the growth of osteophytes around the margins of the vertebral body. Annulus collapse in severe disc degeneration transfers compressive load-bearing to the neural arch, leading to facet joint osteoarthritis, and possibly to degenerative scoliosis. The anterior vertebral body then becomes relatively unloaded, and consequent focal bone loss (exacerbated by systemic osteoporosis) increases the risk of anterior wedge deformities, and senile kyphosis. Future interventions may include physical therapy to aid disc healing, disc prostheses with no moving parts, and injection therapies to block pain pathways.     

终板下椎体缺血诱导兔椎间盘退行性变模型的建立及终板中内皮素1的表达

目的通过终板下注射无水乙醇阻碍椎体-终板营养,建立一种新型兔腰椎椎间盘退行性变模型,并观察终板退行性变过程中内皮素1(ET-1)的表达情况。方法健康4月龄新西兰兔32只,随机分成4组,每组8只,选取L5,6椎体(对应L4/L5及L5/L6椎间盘)注射300μL无水乙醇,选取L4椎体(对应L3/L4椎间盘)注射磷酸盐缓冲液(PBS)作为实验对照,L7椎体(对应L6/L7椎间盘)未注入任何物质作为正常对照。其中1组造模后1个月提取软骨终板细胞,行免疫细胞化学染色检测ET-1表达;余3组分别于造模后1、3和5个月进行椎间盘X线和MRI检查,取椎间盘组织行HE染色观察形态学改变,免疫组织化学染色观察ET-1表达。结果注射无水乙醇后,随着时间进展,X线片显示椎间隙高度显著下降、椎间隙变窄、边缘骨赘增生,MRI T2WI显示椎间盘低信号;苏木精-伊红染色(HE)显示终板的生长板厚度变薄,终板结构破损,同时软骨终板细胞退化、直至消失,髓核中细胞发生转化(由空泡细胞转变为软骨样细胞,进而形成纤维软骨样细胞)造成髓核纤维化,纤维环结构排列紊乱、纤维化程度逐步加重;免疫组织化学染色显示,发生退行性变的终板组织内有ET-1表达,但随着退行性变加剧,ET-1表达强度下降;提取的退行性变软骨终板细胞(造模后1个月)也显示细胞质内ET-1强表达。结论通过注射无水乙醇阻碍椎体-终板营养途径可成功建立兔椎间盘退行性变模型,终板退行性变过程中伴随ET-1的表达。     

Mechanobiology of the intervertebral disc and relevance to disc degeneration

Mechanical loading of the intervertebral disc may contribute to disc degeneration by initiating degeneration or by regulating cell-mediated remodeling events that occur in response to the mechanical stimuli of daily activity. This article is a review of the current knowledge of the role of mechanical stimuli in regulating intervertebral disc cellular responses to loading and the cellular changes that occur with degeneration. Intervertebral disc cells exhibit diverse biologic responses to mechanical stimuli, depending on the loading type, magnitude, duration, and anatomic zone of cell origin. The innermost cells respond to low-to-moderate magnitudes of static compression, osmotic pressure, or hydrostatic pressure with increases in anabolic cell responses. Higher magnitudes of loading may give rise to catabolic responses marked by elevated protease gene or protein expression or activity. The key regulators of these mechanobiologic responses for intervertebral disc cells will be the micromechanical stimuli experienced at the cellular level, which are predicted to differ from that measured for the extracellular matrix. Large hydrostatic pressures, but little volume change, are predicted to occur for cells of the nucleus pulposus during compression, while the highly oriented cells of the anulus fibrosus may experience deformations in tension or compression during matrix deformations. In general, the pattern of biologic response to applied loads suggests that the cells of the nucleus pulposus and inner portion of the anulus fibrosus experience comparable micromechanical stimuli in situ and may respond more similarly than cells of the outer portion of the anulus fibrosus. Changes in these features with degeneration are critically understudied, particularly degeneration-associated changes in cell-level mechanical stimuli and the associated mechanobiology. Little is known of the mechanisms that regulate cellular responses to intervertebral mechanobiology, nor is much known with regard to the precise mechanical stimuli experienced by cells during loading. Mechanical factors appear to regulate responses of the intervertebral disc cells through mechanisms involving intracellular Ca(2+) transients and cytoskeletal remodeling that may regulate downstream effects such as gene expression and posttranslational biosynthesis. Future studies should address the broader biologic responses to mechanical stimuli in intervertebral disc mechanobiology, the involved signaling mechanisms, and the apparently important interactions among mechanical factors, genetic factors, cytokines, and inflammatory mediators that may be critical in the regulation of intervertebral disc degeneration.     

The distribution of surface strain in the cadaveric lumbar spine

The fourth lumbar vertebrae and L4-5 discs from six cadaveric lumbar spines were subjected to detailed strain gauge analysis under conditions of controlled loading. With central compression loads, maximal compressive strain was found to occur near the bases of the pedicles and on both superficial and deep surfaces of the pars interarticularis, which emphasises the importance of the posterior elements of lumbar vertebrae in transmitting load. Radial bulge and tangential strain of the disc wall were maximal at the posterolateral surface, in agreement with the fact that disc degeneration and prolapse commonly occur there. Under posterior offset loads simulating extension, both compressive and tensile strains were found to be increased on both surfaces of the pars interarticularis, which suggests that hyperextension may lead to stress fractures and spondylolisthesis. Posterior offset loads also increased the radial bulge of the posterior disc wall and tangential strain at the anterior surface of the disc. Anterior offset loads simulating flexion increased the radial bulge of the anterior disc wall and tangential strain at the posterior surface of the disc. These findings are compatible with movement of the nucleus pulposus within the disc during flexion and extension. This hypothesis was supported by post-mortem discography.