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Interleukin 1 polymorphisms and intervertebral disc degeneration.

BACKGROUND: Enzymatic breakdown of the extracellular matrix, and possibly local inflammation, contributes to intervertebral disc degeneration. We investigated whether polymorphisms within the IL-1 gene locus are associated with lumbar disc degeneration and whether the effect of occupational physical load on disc degeneration is modified by the polymorphisms. METHODS: Genotypes were determined from 133 middle-aged men who underwent magnetic resonance imaging of the lumbar spine. The participants represented 3 occupations: 40 were machine drivers, 42 carpenters, and 51 office workers. We evaluated decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration in the L2/L3-L5/S1 discs. RESULTS: The odds ratio for disc bulges was 2.4 (95% confidence interval = 1.2-4.8) and 1.9 (1.0-3.7), in carriers of the IL-1alphaT or IL-1betaT alleles, respectively. The TT genotype of the IL-1alpha gene carried more than 3-fold risk of disc bulges as compared with the CC genotype. CONCLUSIONS: IL-1 gene cluster polymorphisms could affect the risk of disc degeneration. The effect of physical workload seems to be modified by the IL-1 gene polymorphisms.

Adult↗

Cervical spinal angiography in midline spondylosis and herniations of intervertebral discs.

Three patients with clinical evidence of cervical myelopathy and degenerative osteoarthritis or herniation of intervertebral disc were studied with angiography. Angiography yielded information regarding the level of the most significant lesion better than did Pantopaque myelography when multiple lesions were present. Angiography also aided in differentiating hard central osteophytic from soft tissue encroachment on the spinal cord caused by herniation of a disc or thickening of the posterior longitudinal ligament. An occasional patient with cervical discogenic myelopathy suggested at multiple levels by myelography may benefit from the localization offered by angiography.

Adult↗

Intradiscal electrothermal therapy can alter compressive stress distributions inside degenerated intervertebral discs.

STUDY DESIGN: Mechanical testing of cadaveric motion segments. OBJECTIVES: To test the hypothesis that intradiscal electrothermal therapy (IDET) can affect the internal mechanical functioning of lumbar discs. SUMMARY OF BACKGROUND DATA: The clinical efficacy of IDET is variable, and its mode of action uncertain. METHODS: Eighteen lumbar motion segments (64-97 years old) were incubated at 37 degrees C. A miniature pressure transducer, side mounted in a 1.3-mm diameter needle, was used to measure the distribution of compressive "stress" along the midsagittal diameter of each disc while it was compressed at 1.5 kN. Measurements were repeated in 3 simulated postures. Standard IDET was performed using biplanar radiography to confirm the placement of the heating element and an independent thermocouple to measure temperature in the inner lateral anulus. Stress profilometry was repeated immediately after IDET. RESULTS: Peak temperatures in the inner lateral anulus during IDET averaged 40.0 degrees C (standard deviation [STD] 2.3). Stress measurements repeated before IDET differed by less than 8%, and a sham IDET procedure produced no consistent changes. After IDET, pressure in the nucleus decreased by 6% to 13% (P < 0.05), and stress concentrations in the anulus were reduced by an average 0.28 MPa (P < 0.004). In 12 of the 18 specimens, anulus stress concentrations were reduced by more than 8%, and in these "responders," mean reduction was 78%. Stress concentrations were increased by more than 8% in 2 specimens. CONCLUSIONS: IDET has a significant but inconsistent effect on compressive stresses within intervertebral discs. These results may partly explain the variable clinical success of IDET.

Aged↗

A one-dimensional theoretical prediction of the effect of reduced end-plate permeability on the mechanics of the intervertebral disc.

The permeability of the cartilage end-plate (CEP) may play an important role in intervertebral disc (IVD) degeneration by controlling the convective and diffusive transport of metabolites into the nucleus pulposus. A one-dimensional poroelastic model was used to predict the effect of a CEP of lower permeability than the disc tissue on the convective transfer into and out of the IVD. With decreasing CEP permeability, associated with degeneration, the model predicted that the change in disc height with time became more linear; the disc could not rehydrate as quickly; and internal fluid movement was slowed. This study has shown that CEP permeability will only markedly have an effect on fluid movement, and hence convective nutrition, if the permeability of the CEP is reduced to less than that of the disc tissue.

Animals↗

Stab incision for inducing intervertebral disc degeneration in the rat.

STUDY DESIGN: The degenerative response of rat tail and lumbar intervertebral discs to a stab incision was evaluated. OBJECTIVE: To examine and compare the postinjury degenerative response of lumbar and tail discs. SUMMARY OF BACKGROUND DATA: Although successful in larger animals, a stab incision for inducing disc degeneration in rats has not been evaluated. Rodents are desirable models for disc repair studies due to their low cost, ease of care, and fast healing times. METHODS: Lumbar and tail discs were exposed surgically and stabbed with a number 11 blade. Disc architecture, levels of IL-1beta, IL-6, and TNF-alpha, and biomechanical properties were analyzed. A functional disability secondary to multilevel lumbar disc injury was quantified and compared with that of rats undergoing sham surgery. RESULTS: Histologic evaluation of stabbed tail discs demonstrated a nucleus pulposus size decrease, anular collagen layer disorganization, and cellular metaplasia of anular fibroblasts to chondrocyte-appearing cells. Besides the continued presence of the stab injury tract, few changes were observed in the lumbar disc histology. Cytokine measurements indicated a transient peak in IL-1beta in tail discs 4 days following injury. No significant changes in IL-1beta, IL-6, or TNF-alpha were measured. No significant differences in biomechanical properties were observed between stab injury and sham surgery discs. Yet, despite insignificant differences in histologic, cytochemical, or biomechanical properties in the lumbar discs, the rats with lumbar stab injury had a significant decrease in walking ability 28 days after surgery. CONCLUSIONS: Tail disc stab injury was successful in creating morphologic signs of degeneration and transient high concentrations of IL-1beta. However, the degenerative response in the lumbar discs was much slower, suggesting that site-specific factors, such as increased stability due to posterior elements and torso musculature, helped facilitate healing. Yet, functional assessment indicated that the rats were partially disabled by multiple lumbar injuries.

Animals↗

[A clinicopathological study of cervical intervertebral discs--Part 1: On histopathological findings].

In order to examine the aging process of the cervical intervertebral discs, a histopathological study was performed on 158 cervical discs obtained at autopsy from 37 individuals ranging in age from 3 months to 87 years. In the nucleus pulposus, degenerative changes consisting of myxomatous and slightly hyalinized degeneration were already seen in the specimens obtained from subjects in the third decade of life. Degenerative changes of the annulus fibrosus, however, tended to develop from the fourth decade of life, with myxomatous degeneration mainly in the anterior and hyalinized degeneration in the posterior annulus. The horizontal fissure of the annulus extending to its outer portion was seen more frequently in the posterior portion. In the cartilaginous plate of the vertebral body, fissure formation and degeneration became evident in the fifth decade of life. In contrast to the disc, repairing processes were observed in the cartilaginous plate. Spur formation at the corner of the vertebral body may be due to the degeneration of the outer layer of the disc leading to enchondral ossification.

Adolescent↗

Integrin expression in cells of the intervertebral disc.

In this study, we investigated the profile of integrin expression in human and porcine intervertebral disc tissue. Differences in extracellular matrix composition between anulus fibrosus (AF) and nucleus pulposus (NP) regions of the disc, as well as differences in cellular responses to environmental stimuli, suggest a role for integrins in presenting matrix signals that may mediate these responses. Human disc tissue and porcine AF and NP tissue were stained with antibodies to alpha integrin subunits 1-6, V and IIb, and beta integrin subunits 1-6 and graded for evidence of positive staining on a scale from 0 (no staining) to 3 (high incidence of staining). Human tissue expressed alpha and beta integrin subunits shown to be present in articular cartilage, including alpha(1), alpha(5) and alpha(V). Porcine AF tissue expressed similar integrin subunits to human disc, with both expressing alpha(1), alpha(5), beta(1), beta(3) and beta(5) subunits, whereas porcine NP tissue expressed higher levels of alpha(6), beta(1) and beta(4) than AF tissue. The expressed subunits are known to interact with proteins including collagens, fibronectin and laminin; however, additional studies will be required to characterize the interactions of the integrin subunits with specific matrix constituents, as well as their specific involvement in regulating environmental stimuli.

Animals↗

A constitutive modeling of the human lumbar intervertebral disc and forward-backward bending simulation.

This paper presents a constitutive law of the lumbar intervertebral disc to be described mathematically with the finite deformation theory. Mechanical behavior of the cadaveric lumbar disc obtained from continuous cyclic compression-tension tests and continuous cyclic axial torsion tests was formulated by the constitutive equation with a semi-circular shaped model. These equations were formulated with or without taking the nucleus pulposus into account. It was also confirmed that forward-backward bending behavior of the disc could be simulated numerically from these equations.

Biomechanical Phenomena↗

[The study of the role of intervertebral disc neovascularization and immune response in the pathogenesis of lumbar discopathy].

In adult humans moral intervertebral disc (id) is an avascular tissue and becomes so called sequestrated autoantigen. Any acquired defect of anulus fibrosus may potentially lead to contact of immunocompetent cells circulating in the blood with id antigens thus inducing autoimmune reaction. 34 patients operated on because of lumbar discopathy were studied. The id injury was divided into: a) protrusion, B) simple prolapse, c) subligamentous prolapse, d) sequester. The samples of surgically removed id were subjected to histopathological and immunohistochemical study. Presence of granulation tissue, neovascularization and humoral response (confirmed by immunopositive reaction to factor VIII and IgG) was found in decreasing pattern in the following groups: I) sequesters, 2) simple prolapses, and 3) subligamentous prolapses. Among protrusions there were only two cases positive for IgG. A negative reaction to C3bR was seen in all the groups of id. The obtained results suggest that immune reaction against lumbar id is rather an effect than a cause of its herniation.

Adult↗

A comparative analysis of the differential spatial and temporal distributions of the large (aggrecan, versican) and small (decorin, biglycan, fibromodulin) proteoglycans of the intervertebral disc.

This study provides a comparative analysis of the temporal and spatial distribution of 5 intervertebral disc (IVD) proteoglycans (PGs) in sheep. The main PGs in the 2 and 10 y old sheep groups were polydisperse chondroitin sulphate and keratan sulphate substituted species. Their proportions did not differ markedly either with spinal level or disc zone. In contrast, the fetal discs contained 2 slow migrating (by composite agarose polyacrylamide gel electrophoresis, CAPAGE), relatively monodisperse chondroitin sulphate-rich aggrecan species which were also identified by monoclonal antibody 7-D-4 to an atypical chondroitin sulphate isomer presentation previously found in chick limb bud, and shark cartilage. The main small PG detectable in the fetal discs was biglycan, whereas decorin predominated in the 2 and 10 y old IVD samples; its levels were highest in the outer annulus fibrosus (AF). Versican was most abundant in the AF of the fetal sheep group; it was significantly less abundant in the 2 and 10 y old groups. Furthermore, versican was immunolocalised between adjacent layers of annular lamellae suggesting that it may have some role in the provision of the viscoelastic properties to this tissue. Versican was also diffusely distributed throughout the nucleus pulposus of fetal IVDs, and its levels were significantly lower in adult IVD specimens. This is the first study to identify versican in ovine IVD tissue sections and confirmed an earlier study which demonstrated that ovine IVD cells synthesised versican in culture (Melrose et al. 2000). The variable distribution of the PGs identified in this study provides further evidence of differences in phenotypic expression of IVD cell populations during growth and development and further demonstrates the complexity of the PGs in this heterogeneous but intricately organised connective tissue.

Aggrecans↗