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Orientation of the articular processes at L4, L5, and S1. Possible role in pathology of the intervertebral disc.

In the synergistic complex formed by the intervertebral disc and posterior articular processes, the latter play a significant role to protect the disc and block forward movement of the spine. This role is of special importance at the level of the lumbosacral interface whose inclination contributes to increase shearing forces acting on the disc. The orientation of the lumbosacral articular processes modifies the distribution of the mechanical stress acting at their level. The relationship between the orientation of the articular processes and the stress transmitted to the disc was studied by computerized tomography (31 subjects without disc prolapse, 35 subjects with disc prolapse, 110 operative reports). Sagittal orientation of the facet joints, which is consistently more pronounced on the right side, seems to promote the occurrence of disc prolapse at the lumbosacral level.

Humans↗

Interaction between the porcine lumbar intervertebral disc, zygapophysial joints, and paraspinal muscles.

STUDY DESIGN: A porcine model was used to study whether muscular activation in the paraspinal muscles caused by nerve stimulation in the anulus fibrosus of a lumbar intervertebral disc could be altered by saline injection into the zygapophysial (facet) joint. OBJECTIVES: To elucidate possible mechanisms regarding the nerve pathways and interactions between the intervertebral disc, zygapophysial joints, and the paraspinal musculature. SUMMARY OF BACKGROUND DATA: The physiologic basis for chronic low back pain, including muscular spasm, is uncertain. Although extensive research involving the lumbar motion segments and the surrounding tissues has been performed, the neuromuscular connection has not been sufficiently investigated. MATERIALS AND METHODS: Twenty-three adolescent pigs were used to measure the electromyographic response in the paraspinal musculature to electrical stimulation of the posterolateral L3-L4 anulus fibrosus, before and after introduction of physiologic saline into the zygapophysial joint. Motor unit action potentials were recorded using three sets of needle electrodes placed into the deepest fascicles of the multifidus, bilateral to the L4 and L5 spinous processes, and into the central longissimus musculature, bilateral to the L4 spinous process. RESULTS: Stimulation of the nerves within the posterolateral anulus of the disc elicited reactions in the paraspinal muscles, namely the lumbar multifidus and longissimus. Introduction of physiologic saline into the zygapophysial joint resulted in a reduction in the motor unit action potential amplitude. This reduction was manifested as an immediate and constant reduction, a graded reduction, or a delayed reaction, during which the reduction occurred an average of 5 minutes after the saline injection. CONCLUSIONS: Introduction of physiologic saline into the zygapophysial joint reduced the stimulation pathway from the intervertebral disc to the paraspinal musculature. The zygapophysial joints may therefore have a regulating function, controlling the intricate neuromuscular balance in the lumbar motion segment.

Action Potentials↗

Galectin-3 expression in the intervertebral disc: a useful marker of the notochord phenotype?

STUDY DESIGN: Galectin-3 expression in rat intervertebral disc at different stages in postnatal life is evaluated. OBJECTIVE: To determine if galectin-3 expression is confined to cells of the nucleus pulposus in the postnatal rat intervertebral disc. SUMMARY OF BACKGROUND DATA: During embryonic development, the anulus fibrosus is derived from the sclerotome, whereas the nucleus pulposus is notochordal. Many authorities opine that in the postnatal disc, notochordal cells play a central role in controlling the development of degenerative disc disease. Surprisingly, unequivocal evidence supporting the existence of notochordal cells in the nucleus pulposus in postnatal life has yet to be demonstrated. Since the expression of galectin-3 is commonly used to identify notochordal cells, we evaluated its expression in tissues of the rat disc and in cultured cells. METHODS: Galectin-3 expression was studied in the nucleus pulposus and anulus fibrosus tissue of rat discs (2 days, 9 weeks, and 10 months old), and cultured cells using different biochemical and molecular biology methods. Rat sternal cartilage and cultured sternal chondrocytes were used as controls. RESULTS: Immunohistochemical studies indicated that galectin-3 was present in the nucleus pulposus and anulus fibrosus. In both discal tissues and cultured cells, studies confirmed that there was a robust expression of galectin-3 messenger ribonucleic acid and protein. Protein expression patterns were similar in neonatal, young, and mature rats. There was also evidence of intracellular and membrane expression of galectin-3 in the cultured disc cells. Finally, significant levels of galectin-3 were evident in rat sternal cartilage and cultured sternal chondrocytes. CONCLUSIONS: Results of the study indicate that galectin-3 is expressed in the neonatal, young, and mature rat disc, and its expression is not restricted to the cells of the nucleus pulposus. Because of its ubiquitous expression, this protein cannot be used as a marker of notochordal cells in the postnatal rat disc.

Aging↗

Degeneration of intervertebral discs due to smoking: experimental assessment in a rat-smoking model.

We have investigated the intervertebral discs of rat-smoking models to demonstrate that smoking is a cause of degenerative intervertebral disc disease. A smoking box was developed for this study. We exposed 8-week-old rats to indirect tobacco smoke inhalation. Each rat was forced to inhale the smoke from one cigarette per hour. The mean blood nicotine level of rodents exposed to cigarette smoke corresponds to about twice that of ordinary human smokers. Histological and immunological studies were then performed to assess the effects of smoking for varying periods of time. After 8 weeks, the chondrocytes in the disordered annulus fibrosus layer tended to grow larger and attain a rounder form than normal chondrocytes. The interleukin-1beta level in the 8-week smoking group was significantly higher than that of the control group. Tobacco smoke inhalation increased local production and release of inflammatory cytokines and resultant decomposition of chondrocyte activity.

Animals↗

Levels of keratan sulfate-bearing fragments rise predictably following chemonucleolysis of dog intervertebral discs with chymopapain.

Chymopapain (1 mg) was injected into each of four-lumbar intervertebral discs of adult mongrel dogs. As expected, at 2 weeks, all injected discs exhibited marked loss of height (mean: 50% of original height) indicative of severe proteoglycan depletion. The appearance of keratan sulfate-bearing fragments in plasma was monitored by an ELISA-inhibition assay which uses a monoclonal antibody (1/20/5-D-4) specific for an epitope present only in the longest keratan sulfate chains. Levels of plasma keratan sulfate rose within 30 minutes and reached a maximum between 24 and 72 hours later. Levels then declined progressively but were still elevated at 2 weeks postinjection. Keratan sulfate-bearing fragments in plasma were purified by ion exchange chromatography on DEAE-Sephacryl and fractionated by sieve chromatography on Sepharose CL-6B. These plasma keratan sulfate-bearing fragments were found to be similar in size to keratan sulfate-bearing fragments generated by chymopapain digestion of dog nucleus pulposus proteoglycans, but slightly larger than single keratan sulfate chains obtained by alkaline borohydride treatment of dog nucleus pulposus proteoglycans. The results of this study show that measurements of blood levels of keratan sulfate could prove useful in monitoring effective degradation of disc proteoglycans in chemonucleolysis in man and help discriminate between ineffective enzyme placement, and alternative mechanisms of treatment failure.

Animals↗

A surgical technique for a vertebral column autograft using the intervertebral disc for cervical disc disease.

We describe a surgical technique for a vertebral column autograft using the intervertebral disc for cervical disc disease for patients whose major problem is not spinal instability. Of a total of 41 patients with cervical disc disease suffering from cervical spondylotic radiculomyelopathy, 33 patients were operated on at one level and 8 patients were operated on at two levels. Postoperative X-ray film showed some movement at the "operated" disc level in all patients (average postoperative follow-up period was 43 months, range two years to 5 years). A significant decrease in motion in the extension position was observed postoperatively (p < 0.0001), but no significant difference was observed between the preoperative motion and the postoperative motion in the flexion position. Anterior angulation was found in two (5%) of the 41 patients. This surgical procedure has two major advantages: 1) no complications related to the iliac donor site, allowing early patient mobilization; 2) the extensive posterior spur can be removed safely and easily under a wide operative field. We believe that this surgical procedure is suitable for preserving the mobility of the spine and may avoid stress concentration at adjacent levels of the "operated" disc. However, in patients whose major problem is spinal instability, anterior cervical fusion should be performed.

Adult↗

Natural history of paediatric intervertebral disc calcification.

This case report concerns a 5-year-old boy who had intervertebral disc calcification with involvement of two disc spaces and herniation of nucleus pulposus in one. The patient's symptoms resolved completely in a week with conservative measures. At the 4-year follow-up, the child was symptom-free and in full health, the herniation of nucleus pulposus had resolved completely, and calcification had disappeared in one of the disc spaces. Although the cause of this disorder is uncertain, the course is benign and self-limiting, it seldom requires surgical intervention, and the natural history is one of resolution and complete resorption of the calcification.

Calcinosis↗

IL-1beta sensitizes intervertebral disc annulus cells to fluid-induced shear stress.

Chronic inflammation and altered mechanical loading are implicated as contributors to intervertebral disc degeneration. Biomechanical and biochemical factors play a role in disc degeneration but have received limited study. Mechanically, intervertebral discs are sheared during bending or twisting of the trunk. Biochemically, IL-1beta, detected in degenerative discs, promotes metalloproteinase expression. We hypothesized that disc cells might respond to shear stress and IL-1beta in a calcium signaling response. We measured the effect of single and combined stimuli on intracellular calcium concentration ([Ca2+]ic) and signaling. Cells were isolated from annulus tissue, cultured to quiescence, plated on collagen-bonded Culture Slips and incubated with Fura-2AM. Cells then were incubated in IL-1beta. Cell response to the effects of fluid flow was tested using FlexFlo, a laminar flow device. Human annulus (hAN) cells responded to laminar fluid flow with a one to three-fold increase in [Ca2+]ic. IL-1beta alone produced a small, transient stimulation. hAN cells pretreated with IL-1beta responded to shear with a more dramatic and sustained increase in [Ca2+]ic, six to ten-fold over basal level, when compared to shear then IL-1beta or shear and IL-1beta alone (P<0.001 for all comparisons). This is the first study documenting synergism of a signaling response to biomechanical and biochemical stimuli in human disc cells. IL-1beta treatment appeared to "sensitize" annulus cells to mechanical load. This increased responsiveness to mechanical load in the face of inflammatory cytokines may imply that the sensitivity of annulus cells to shear increases during inflammation and may affect initiation and progression of disc degeneration.

Adolescent↗

Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration.

STUDY DESIGN: A study in genetic epidemiology of disc degeneration, based on lifetime exposure data, findings on magnetic resonance imaging, and genotyping of intragenic markers. OBJECTIVES: To pursue the potential correlation between common allelic variations in the vitamin D receptor locus and degeneration of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Familial aggregation has been observed in intervertebral disc degeneration, but the relative significance of the genetic component and shared environmental influences is unknown. The identification of relevant candidate genes associated with disc degeneration would specify a genetic component and increase our understanding of the etiopathogenesis of disc degeneration. METHODS: From the population-based Finnish Twin cohort, 85 pairs of male monozygotic twins were selected based on exposure to suspected risk factors for disc degeneration. Interview data were gathered on relevant lifetime exposures, and thoracic and lumbar disc degeneration was determined through quantitative and qualitative assessments of signal intensity on magnetic resonance imaging, and qualitative assessments of disc bulging and disc height narrowing. Possible associations were examined between disc degeneration measures and two polymorphisms of the coding region of the vitamin D receptor locus. RESULTS: Two intragenic polymorphisms of the vitamin D receptor gene revealed an association with disc degeneration. Quantitatively assessed signal intensities of thoracic and lumbar (T6-S1) discs were 12.9% worse in men with the Taql tt genotype and 4.5% worse in men with the Tt genotype, compared with signal intensity in men with the TT genotype (age adjusted P = 0.003). A similar pattern was found between disc signal intensity and Fokl genotypes; men with the ff and Ff genotypes had mean signal intensities that were 9.3% and 4.3% lower, respectively, than those in men with FF genotypes (age-adjusted P = 0.006). The summary scores of qualitatively assessed signal intensity, bulging, and disc height were 4.0% and 6.9% worse in men with Ff and ff genotypes, respectively, when compared with those in men with the FF genotype (age-adjusted P = 0.029). CONCLUSION: Specific vitamin D receptor alleles were associated with intervertebral disc degeneration as measured by T2-weighted signal intensity, demonstrating for the first time, the existence of genetic susceptibility to this progressive, age-related degenerative process.

Adult↗

Quantitative analysis of gene expression in a rabbit model of intervertebral disc degeneration by real-time polymerase chain reaction.

BACKGROUND CONTEXT: Serial analysis of gene expression during the course of intervertebral disc degeneration (IDD) could elucidate valuable insight into pathophysiology and provide a basis for identification of potential targets for the development of novel cellular- and gene-based therapies. However, very few previous studies described the changes in gene expression through the process of IDD using a suitable animal model. PURPOSE: To use a recently developed rabbit annular stab model and the technique of real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify the change in expression of key rabbit-specific mRNA sequences encoding for selected extracellular matrix (ECM) products, catabolic, anabolic, and anti-catabolic factors in normal and stabbed discs. STUDY DESIGN: Gene expression analyses were performed to characterize a slowly progressive and reproducible animal model of IDD using real-time RT-PCR. METHODS: Twelve rabbits underwent an annular stab with a 16-gauge needle to the L2-L3, L3-L4, and L4-L5 discs, and three rabbits served as sham controls. Nucleus pulposus tissues were harvested from the stabbed discs at 3, 6, 12 and 24 weeks after confirmation of degenerative changes by magnetic resonance imaging (MRI) scan. Real-time RT-PCR was performed with the use of rabbit-specific primers for 1) extracellular matrix (ECM) component genes: collagen type Ia and IIa, and aggrecan; 2) catabolic genes: matrix metalloprotease-3 (MMP-3), inducible nitric oxide synthase (iNOS), and interleukin-1beta (IL-1beta); 3) anabolic growth genes: bone morphogenic protein-2, and -7 (BMP-2, -7), transforming growth factor-beta1 (TGF-beta1), and insulin-like growth factor-1 (IGF-1); and 4) anti-catabolic gene: tissue inhibitor of metalloprotease-1 (TIMP-1). These data were normalized to mRNA levels of glyceraldehyde phosphate dehydrogenase (GAPDH), a constitutively expressed gene. RESULTS: The MRI images confirmed progressive decline in the nucleus pulposus area of high T2 signal and in the signal intensity of the stabbed discs over the 24-week study period consistent with IDD. The ECM components, aggrecan and collagen type IIa mRNA levels had decreased markedly by week 3 and never recovered, whereas type Ia collagen mRNA gradually increased throughout course of degeneration. BMP-2, BMP-7 and IGF-1 mRNA were relatively decreased from weeks 3 to 6 but then increased at weeks 12 and 24 to end at a level near the preoperative level. The TIMP-1 expression fell dramatically to approximately one tenth of the preoperative level by week 3 and remained low throughout the degenerative process. The remaining results, including those from TGF-beta1 and the catabolic genes (MMP-3, IL-1beta, iNOS) demonstrated a double peak characteristic. The gene expression increased by week 3, decreased to a low level at weeks 6 and 12 and then had a second, late peak at 24 weeks. CONCLUSIONS: The gene expression profiles of ECM components and anabolic, catabolic, and anti-catabolic factors demonstrate many characteristics similar to the findings in human disc degeneration and suggest an inability of the intervertebral disc (IVD) to mount an early anabolic response to injury, thereby offering a possible explanation for the disc's lack of reparative capabilities. Catabolic genes are strongly up-regulated both early and late in degeneration, lending strong support to the hypothesis that an anabolic or catabolic imbalance plays a primary role in IDD. According to the resultant patterns, augmenting early production of BMP-2, BMP-7, IGF-1 or TIMP-1 by gene transfer techniques might possibly alter the progressive course of degeneration as seen in the stab model. The next step will be to transfer these therapeutic genes to regulate the biologic processes and ideally alter the progressive course of disc degeneration.

Animals↗

Collagenase-1 and stromelysin distribution in fresh human herniated intervertebral disc: a possible link to the in vivo inflammatory reactions.

Chondrocytes may play an important role in the inflammatory reactions involving intervertebral discs: the role of metalloproteases (MMP) and the imbalance between proteases and their inhibitors seems to play a crucial role in the disc degenerative process. In the present study we have analysed the production of collagenase-1 and stromelysin in different parts of herniated intervertebral discs. Ten samples of herniated lumbar discs were obtained from adult patients operated on for primary microdiscectomy because of persistent radicular symptoms and subdivided into three samples: 1. The nearest to the nerve root in close contact with it, 2. the sample obtained from the intervertebral space, and 3. the sample obtained from the vertebral plates. The DNA content of each specimen was measured in order to obtain the best estimate of the cell content as well as to normalise the content of collagenase-1 and stromelysin found in the same tissues with respect to the number of cells. In 9 out of the 10 cases the DNA content was significantly higher in samples obtained from the intervertebral plates than in samples obtained near the nerve root or the intervertebral space. DNA content did not show any significant difference considering disc samples contiguous to the nerve root and samples obtained from the intervertebral space. The production of collagenase-1 did not show a specific pattern, being produced in similar quantities in the three disc compartments. The production of stromelysin was significantly lower in disc samples obtained from the intervertebral plates. In conclusion the results of the present study suggest firstly that in the herniated lumbar disc the reactivity and the production of pro-inflammatory agents is independent of DNA content, i.e. the cellularity of the sample, and secondly that activated cells in the intervertebral space and in the part of the disc in contact with the nerve root, even if scarce in number, are able to synthesise a proportionally higher quantity of MMP than the high-cellular disc fragments from the intervertebral plates, potentially playing a specific role in the inflammatory reactions.

Adult↗

Immunohistochemical study of chymopapain injected into the rabbit intervertebral disc using anti-chymopapain antibody.

This study was undertaken to investigate the morphological action of chymopapain (CP) in intervertebral discs. Of 20 mature Japanese white rabbits, 19 lumbar intervertebral discs were used for electron microscopic examination, and 36 discs, for immunohistochemical examination. Discs from 3 hours to 8 weeks after injection were observed by light and electron microscopy using anti-CP rabbit antibody labeled with horseradish peroxidase. Using Kagami's DMF-dehydration, two types of fine fibers were observed in the extracellular matrix of normal nucleus pulposus, in addition to collagen fiber. After injection of CP, the thinner fibers disappeared, while the thicker fibers remained. The injected CP spread from the nucleus pulposus to the annulus fibrosus within several hours and remained as long as 4 weeks. By immunoelectron microscopy, positive granules were divided into Type 1 (lacking relationship to collagen fibers) and Type 2 (adhering to or surrounding collagen fibers). The thinner fibers appear to be proteoglycan monomer and are the target for CP.

Animals↗

MRI and discography in traumatic intervertebral disc lesions.

In this study we evaluated magnetic resonance imaging (MRI) in trauma patients for assessing traumatised adjacent discs of fractured vertebrae before dorsoventral stabilisation. In a prospective study, MRI of 54 discs was performed with a 1.5-T MRI unit. The preoperative MRI with sagittal T1-W-SE and T2-W-TSE was compared to intraoperative discography, which was carried out on both intervertebral discs adjacent to the fractured vertebrae. Signal alterations, morphological changes in the adjacent discs, fractured vertebrae and associated ligament injuries were evaluated. In 47/54 (87%) of the intervertebral discs, the results of both imaging findings were concordant. The discs adjoining vertebral fractures were normal in 18 cases. Regarding the positive concordant imaging findings, MRI and discography revealed traumatised adjacent cranial and caudal discs in 22 discs. In 7 cases, only the cranial adjacent disc was affected. Moreover, 17 cases of intradiscal bleeding, 13 intraosseous herniations into the fractured vertebrae and 20 anuluar tears were visualised in MRI. Associated ligament injuries were detected in 18 cases. Findings were discordant in eight discs. In six discs, MRI was abnormal, demonstrating signal alterations suggestive of positive imaging findings, whereas discography demonstrated no disc injury. MRI failed to detect disc injury in two discs, whereas discography was positive, showing an irregular intradiscal contrast media distribution. MRI, as a non-invasive method for assessing fractures of the thoraco-lumbar spine, may detect traumatised adjacent intervertebral discs. MRI is superior to intraoperative discography. The performance of MRI of the thoraco-lumbar spine is recommended before dorsoventral stabilisation in trauma patients, as it can reveal additional preoperative information such as fractures, disc and associated ligament injuries.

Adolescent↗

Flow-related mechanics of the intervertebral disc: the validity of an in vitro model.

STUDY DESIGN: An in vitro mechanical study on porcine motion segments. OBJECTIVES: To test the validity of in vitro studies of the flow-related mechanics of the intervertebral disc and, in particular, to investigate whether fluid flows back into the disc during unloading after a loading cycle. SUMMARY OF BACKGROUND DATA: In vivo studies show both the inflow and outflow of fluid in the intervertebral disc. The resistance to flow out of the disc is higher than to inflow. The fluid flow is regulated via unbalance between the external load and the osmotic pressure of the nucleus pulposus. MATERIALS: There were 8 porcine lumbar motion segments (without posterior elements) and 8 isolated discs tested in a physiologic saline bath (39 degrees C). The specimens were preloaded at 0.025 MPa for 15 minutes. Three 15-minute loading periods at 2.0 MPa were applied, each followed by an unloading period of 30 minutes. Loads, axial displacements, and nucleus pressure were recorded online. RESULTS: Over the 3 loading and unloading periods, all specimens showed a net loss of height and mass. The time series of specimen height during the 3 unloading periods showed virtually identical responses. The pressure in the nucleus decreased in the subsequent loading periods and showed no increase during unloading. CONCLUSION: The data show the limitations of an in vitro model for studying fluid flow-related intervertebral disc mechanics. During loading, outflow of fluid occurred, but inflow appears to be virtually absent during unloading. Poro-elastic behavior cannot be reproduced in an in vitro model.

Animals↗

CD44 expression in the developing and growing rat intervertebral disc.

CD44 has been identified at the time of extracellular matrix formation and expansion in several sites of the developing embryo (Wheatley et al. [1993] Development 119:295-306). The nucleus pulposus, consisting of a hydrated extracellular matrix tissue at birth, not previously closely analyzed, was examined for expression of CD44 in the developing and aging rat intervertebral disc. CD44 was identified solely on notochordal cells from the first onset of intervertebral disc formation (day 15 embryo) through the loss of notochordal cells from the nucleus pulposus (12-24 months of age). No CD44 expression was found in the notochordal cells prior to disc formation or in any cells other than the notochordal cells in the annulus fibrosus or nucleus pulposus of the intervertebral disc. Using reverse transcriptase-polymerase chain reaction methodology, the single 365 amino acid CD44 standard, CD44s, open reading frame was amplified from notochordal cells isolated from the nucleus pulposus. Western blot analysis of a cultured nucleus pulposus notochordal cells total protein extract identified a single CD44 species devoid of chondroitin sulfate with a mass of approximately 85 kDa, characteristic of CD44s. Cell surface detection for CD44 was co-localized with hyaluronan and proteoglycans at first appearance of disc formation in the nucleus pulposus.

Animals↗

Histologic characterization of coblation nucleoplasty performed on sheep intervertebral discs.

OBJECTIVE: To characterize the histologic effects of coblation nucleoplasty on sheep intervertebral discs. DESIGN: In vitro histologic study. METHODS: Five sheep lumbar discs treated with nucleoplasty and two control discs were evaluated. Specimens were received frozen and thawed to room temperature. A segment consisting of the intervertebral disc and vertebral body above and below the disc was dissected. Using a posterolateral approach, a Perc-DLE SpineWand attached to a standard radiofrequency power generator was bluntly advanced to the annulonuclear junction of each disc. The SpineWand was advanced initially in cauterization mode 8mm into the disc and withdrawn in coagulation mode. The SpineWand was reinserted 8mm into the disc and secured in place. The specimens were fixed in 10% buffered formalin for 1-2 weeks. They were then decalcified in 10% ethylenediaminetetraacetic acid (EDTA) and embedded in paraffin. Specimens were subsequently stained with H & E, Alcian Blue, and Trichrome stain. They were examined under light microscopy and polarized light. RESULTS: There were no gross changes in disc appearance. In the experimental disc, the fenestration created by the procedure left a 1mm diameter hollow channel through which tissue was cauterized leaving little visible debris or residual material. In the area immediately surrounding the channel, the fibrocartilage cells and the collagen matrix arrangement remained intact and resembled the control untreated disc tissue. There was no loss or re-distribution of proteoglycans, no alterations in collagen orientation, nor any indication of damage to the matrix surrounding the probe channel. CONCLUSION: Radiofrequency nucleoplasty creates a hollow channel leaving surrounding soft tissue intact in the immediate post-procedure period. In vivo studies will be necessary to delineate the longitudinal histologic effects of radiofrequency nucleoplasty on discs.

Journal Article↗

Age-related changes in expression of transforming growth factor-beta and receptors in cells of intervertebral discs.

OBJECT: The authors conducted a study to determine age-related changes in expression of transforming growth factor (TGF)-beta1, -beta2, -beta3, and Type I and Type II receptors in various cells in the nucleus pulposus and anulus fibrosus. Immunolocalization of TGFbetas and Type I and II receptors was examined during the aging process of cervical intervertebral discs in senescence-accelerated mice (SAM). The TGFbeta family has important roles for cellular function of various tissues. Its role in disc aging, however, is unknown. Detailed information on the temporal and spatial localization of TGFbetas and their receptors in discs is required before discussing introduction of them clinically into the intervertebral disc. METHODS: Three groups of five SAM each were used. The groups of SAM were age 8, 24, and 50 weeks, respectively. Hematoxylin and eosin staining and immunohistochemical study involving specific antibodies for TGFbeta1, -beta2, -beta3, and Types I and II TGF receptors were performed. Intervertebral discs exhibited degenerative change with advancing age. The TGFbetas and their receptors were present in the fibrocartilaginous cells within the anulus fibrosus and notochord-like cells within the nucleus pulposus of young mice. Expression of TGFbetas and Type I and Type II receptors changed markedly in the cells within the anulus fibrosus during the aging process. CONCLUSIONS: The TGFbetas and their receptors were present in cells within the nucleus pulposus and the anulus fibrosus of young mice, and their expression decreased with age.

Aging↗

Mechanical conditions that accelerate intervertebral disc degeneration: overload versus immobilization.

STUDY DESIGN: A review of the literature on macromechanical factors that accelerate disc degeneration with particular focus on distinguishing the roles of immobilization and overloading. OBJECTIVE: This review examines evidence from the literature in the areas of biomechanics, epidemiology, animal models, and intervertebral disc physiology. The purpose is to examine: 1) what are the degeneration-related alterations in structural, material, and failure properties in the disc; and 2) evidence in the literature for causal relationships between mechanical loading and alterations in those structural and material properties that constitute disc degeneration. SUMMARY OF BACKGROUND DATA: It is widely assumed that the mechanical environment of the intervertebral disc at least in part determines its rate of degeneration. However, there are two plausible and contrasting theories as to the mechanical conditions that promote degeneration: 1) mechanical overload; and 2) reduced motion and loading. RESULTS: There are a greater number of studies addressing the "wear and tear" theory than the immobilization theory. Evidence is accumulating to support the notion that there is a "safe window" of tissue mechanical conditions in which the discs remain healthy. CONCLUSIONS: It is concluded that probably any abnormal loading conditions (including overload and immobilization) can produce tissue trauma and/or adaptive changes that may result in disc degeneration. Adverse mechanical conditions can be due to external forces, or may result from impaired neuromuscular control of the paraspinal and abdominal muscles. Future studies will need to evaluate additional unquantified interactions between biomechanics and factors such as genetics and behavioral responses to pain and disability.

Animals↗